Leishmania

Student guest post: Unintended Consequences

tsmith — Mon, 17 Jun 2013 18:00:53 +0000

Student guest post: Unintended Consequences

Student guest post by Naomi Kirschenbaum

Although we can never know, there are estimates in the range of 15,000 displaced pets in the wake of 2005 Hurricane Katrina. Many of the dogs found their way to shelters and homes in our community around the Monterey Bay in California. As a local veterinarian the most notable observation I saw was how it “seemed” that so many were heartworm positive. Six years later we have a published study finding a 48.8% prevalence of heartworm in these dogs.

This story is an example of a few important lessons. First, how things seemed to me, in my clinical practice turned out to be 48.8% of the dogs, not all. (Of course in our area we may have had a different subset of positive dogs, but I thought, in general, they were nearly all heartworm positive). Secondly, how long it takes for a study to be done and published. In this case the study I referenced has a six year interval between the event and publication of data examining an aspect of concern.

Now, let’s step into the present. I’m currently taking courses for a Masters in Public Health at the University of Iowa to branch out from my basic training in veterinary medicine.

Yesterday, in a course I’m taking we had a lecture on a group of zoonotic diseases, Trypanosomes. This group of little single celled organisms, protozoans, causes problems all over the world. In Africa it causes, Sleeping Sickness, in Latin America, Chagas’ disease. We don’t hear a lot about it here in North America.

What came to my attention was a disease described in dogs, here, in the U.S. caused by one in this group called Leishmania. Dogs are a known reservoir in areas where these diseases are endemic but these U.S. reports starting in the late 1990’s were in two breeds with whopping over representation, specifically Foxhounds¹ and Neapolitan Mastiffs.

That’s weird, I thought. I’ve been a small animal veterinarian for a long time and those are not two very common breeds. What’s up?

The first two things you need to know have to do with our basic understanding of where this parasite lives and how it infects mammals. It has been traditionally thought a mammal becomes infected from the bite of an insect vector (tsetse fly in Africa or sand fly in South America), which is carrying the protozoa. Also, although this occurs more rarely, you can become infected by direct contact with the blood of an infected animal into your tissue, read blood-to-blood transmission. This second bit of information will be important later.

As well from studying these outbreaks in Foxhounds, one research group received a donated pregnant bitch they new was infected which allowed them to examine the puppies and look to see if they were also infected. They found Leishmania in the puppies. This lends evidence of transmission of the organism from mother to puppies in utero. Their thought is the Leishmania protozoan circulates in the mother’s blood and crosses over the placenta to infect the developing fetuses.

An important point here is the novel idea that transmission of the infection can be vertical and DOES NOT REQUIRE A VECTOR. This would mean you could sustain the parasite in a mammal population where it has never lived before and would not normally be expected to be able to live.

This disease is endemic in parts of Europe and these two breeds, although fairly rare here in the U.S., often are imported from Leishmania endemic areas to be incorporated into U.S. breeding stock lines. These imported dogs are very valuable and key to their breeding programs.

The work done showing vertical transmission from mother to pup suggests we can establish the infectious agent in a host indefinitely. So far we are lucky and the areas where these dogs live don’t have vector insects readily available. I wouldn’t count on that lasting too long. Between global travel and climate change alone, and if historical record of disease spread with so many other zoonotic infectious agents is any guide, it’s really, likely, just a matter of time.

So a final concern, more immediate, goes back to that second route of traditional transmission I described above, the direct contact, blood-to-blood infection. Here’s the thing. These dogs, the Foxhounds and Neapolitan Mastiff’s that are infected are breeding dogs. Breeding dogs, by definition, are sexually intact. Dogs that have their “parts” can more often get into scrapes (read: fights). When dogs fight they really can tear each other up. The fighting often occurs around the head, neck and ears. All fight wounds bleed, a lot. Ears especially bleed like stuck pigs.

People try to break up the fighting dogs. People get bitten all the time doing this. (Read: Do not try to break up fighting dogs yourself, but that’s another essay of it’s own). The dog blood that is all over the dogs is now all over you. You have an open bite wound. The dog’s blood now is mingling with your tissue and blood. You now have Leishmania. This is the problem.

The good news is if you are immune-competent you should mount a good response to this insult and have a very good likelihood of clearing the infection. It will require a significant effort calling upon both arms of your immune systems, the cellular and the humoral. Unfortunately you will not be immune to reinfection should another exposure event occur. The bad news is if you are in anyway immune compromised, not so good. You are likely to get clinical illness.

I guess our best hope at this point in time is to help breeders see the need and importance of choosing disease free dogs. Encourage them to buy and bring only dogs that they have tested and know are free of Leishmania into the U.S. I know breeding for phenotype and working characteristics and abilities is the holy grail of breeders, but can’t we do it looking at the bigger picture, the greater good?

¹Monti, Dean (June 2000). "Hunters hounded as leishmaniasis is diagnosed in Foxhounds". J Am Vet Med Assoc 216 (12): 1887, 1890.

tsmith Mon, 06/17/2013 - 14:00

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

cwilcox — Mon, 24 Aug 2009 09:14:00 +0000

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., & MÃ¼ller, 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 MemÃ³rias do Instituto Oswaldo Cruz, 102 (5) DOI: 10.1590/S0074-02762007005000070

cwilcox Mon, 08/24/2009 - 05:14