Parastic LIfe Cycles and Parasitic Infections
Chris - Now you're a parasitologist, so how the hell did you get into studying parasites? Did you get some horrendous worm infection as a youngster that got you interested in this or something?
Mark - No it's more academic than that. I was an undergraduate student at Imperial College in London and part of my third year course was all about parasites and I thought ooh, these are rather fascinating creatures.
Chris - But in particular you focus on this thing called schistosomiasis and we'll come to that in just a second. But we say that if you've got lots of parasites around then you must have a healthy population. Is that true?
Mark - Probably not. Lots of parasites certainly are a big problem. Nowadays there's certainly a change in people's thinking in that some parasites may be good for you, but a lot of the parasites are bad for you.
Chris - Now one of the focuses of Mark's work is this thing called schistosomiasis, which is also called bilharzia. It's a highly infectious pathogen and we couldn't possibly bring it into the studio. Part of its life cycle is spent in freshwater snails before it gets into humans, so what we asked Mark to do was to go round with me at his lab at Cambridge University on Friday and show us some of the snails that carry it. This is what we found out.
Mark - We're standing in the schistosomiasis research lab, and we're outside the snail room which is where we keep snails that we use to perpetuate the life cycle of Schistosoma mansoni worms. You'll see right in front of us there's a door with a very orange and red biohazard sign on it. That's because the snails in here are infected and if we were to put our fingers in the tanks where we're keeping the snails, we would also be infected with the worms.
Chris - Shall we have a look at them?
Mark - Let's go.
Chris - Well there are literally rows and rows of tanks full of snails. It's quite dark in here, Mark.
Mark - Yes it's deliberately kept dark because these snails tend to shed the parasite when there is bright light, so we keep them artificially under dim conditions, and when we want to shed them we take them out of the tanks we see in front of us, put them into a small beaker and shine a very bright light on them.
Chris - Why should the parasite want to come out when you put light on the snail?
Mark - That's because under natural conditions, the snail tends to shed the parasite when there are people around. People tend to come into contact with the water during daylight hours, so it helps if the parasite is shed when there are people around and the light is very bright.
Chris - So can we have a look at some of these snails because they're quite small aren't they?
Mark - They are indeed. These are Biomphalaria snails that transmit Schistosoma mansoni. So if you look inside the tank, you'll see that they are very small, maybe about a centimetre wide. These are freshwater snails. You'll see also in the tank that there's some vegetation and these are what the snails feed on.
Chris - So the larvae come out of the snail, burrow through my skin, get into me and then where do they go in my body?
Mark - Well they get passively circulated through the blood system, so essentially when they penetrate the skin they locate a blood vessel and are then circulated via the heart into the lungs. They then elongate and mature in the lungs and then are carried back through the heart. In the liver they then sexually mature and actually end up in the mesenteric veins that link the liver to the gut. That's where they couple and start producing the eggs.
Chris - And how do the eggs find their way back out of the human so they can find another one of those snails?
Mark - Well there's a very good reason why worms are located in the mesenteric veins. That's because they are very close to the gut. When the eggs are laid by the female worm they don't have very far to go: they just have to cross the gut wall and then they're passed out with faecal matter.
Chris - So safe handling of sewage and sewage contaminated water is absolutely crucial in breaking this life cycle and preventing this from happening.
Mark - Absolutely. A high standard of hygiene is required.
Chris - Is it feasible to think that we could stop people becoming infected with these things then?
Mark - There are a number of schemes available. There is a very safe and widely used drug called Praziquantel, which is used in major intervention programmes. The problem with Praziquantel is that it doesn't have any vaccination properties that we know of. So what happens is that people who are treated go out the next day, conduct themselves as normal and they get re-infected. The way to stop people getting infected over the long term is to change their environment and also their habits.
Chris - Well that was us in Mark's lab a couple of days ago. So Mark, it's a big problem schistosomiasis. How many people do you think worldwide are affected with this?
Mark - There's an estimate that about 200 million people are infected, but maybe 600 million people live in an area where they're at risk of infection.
Chris - So it is a pretty major problem. But how does that compare with other major parasite infections worldwide?
Mark - It's somewhere in the middle of the rankings. If we look at some other parasites like the roundworm, that maybe affects about a billion people worldwide, and hookworms 800 million, and trichuris infections a few hundred million as well.
Chris - So you mentioned some of these other worms here, they actually get spread by faecal-oral, in other words people picking up things from the environment, don't they?
Mark - Yes, they're also called soil-transmitted helminths and people become infected when they ingest contaminated soil essentially.
Chris - They don't just have to eat them do they, because don't some of these parasites, like you were saying with schistosomiasis, they can actually drill holes in skin and get in that way. Don't some of these other things do that?
Mark - Yeah the hookworms are particularly good at that. The larvae are shed on the soil and they penetrate the skin when people stand on top of them.
Chris - So tell us a little bit about that because these are worms, so how do they end up going through your skin but migrate to the gut subsequently?
Mark - They're able to penetrate the skin using proteases, which are chemicals that actually melt the tissue away. They then get passively circulated through the blood and they will end up in the lungs. They'll often be coughed up, and when they're coughed up they're swallowed and that's how they end up in the gut.
Chris - And once they get into the gut, how do they survive there?
Mark - They seem to do it very well; they can live for many years. This is one of the great questions that has been asked by researchers: how do they exist in that situation?
Chris - Do they eat our food then, these hookworms?
Mark - Hookworms don't. Hookworms will penetrate the gut lining and drink blood from capillaries.
Chris - And I suppose that you probably started to talk about one particular important thing here, which was that all these things manage to get in through skin, they get into the blood stream, they live in lungs or other tissues and make their way to a final resting place in the gut. So how do they escape the immune system? Why doesn't our immune system attack them and stop them?
Mark - Again, a very good question. There's are a great many researchers interested in answering this question. Essentially it's down to a very sophisticated array of evasion strategies. Some parasites will coat themselves with the antigens of the host so they become almost invisible; some parasites live inside the cells of the host so they're essentially not seen by the immune system; and some parasites will subvert the immune system of the host to the parasite's advantage.
Chris - But haven't some people said that that's really really useful because if we can understand how they do that then we might be able to use this to our advantage to switch off allergy and things.
Mark - Yes. As I said at the beginning, there's now a change in people's perception of what parasites are doing, and it's been suggested that some parasites may be good for you because they do down-regulate some of our more harmful immune responses.
Chris - Now what about some of these other parasites that we see that cause horrible diseases like elephantiasis, people with very swollen limbs. What's going on there?
Mark - Elephantiasis is specifically caused by a filarial nematode and the worms live in lymph nodes. They cause blockage of the lymph nodes and they don't allow lymph fluid to drain properly. Now when that happens you get a process called lymphedema started, which generally affects the lower limbs.
Chris - How do you catch it in the first place?
Mark - Filariasis is transmitted by mosquitoes of the culex genus. The mosquito will bite and then inject a larval form of the filarial worm, which will then mature and migrate to the lymph nodes.
Chris - Now you showed me the other day a picture of someone with a rather nasty lesion on their hand that had a white worm coming out of it, and a matchstick winding the worm up. What was that?
Mark - That was a guinea worm or Dracunculus. That's also a nematode and that was a female worm that I showed you and she's emerging from the skin of that person to lay her eggs. She's formed a blister which is very irritable, so the person would have gone to water to soothe the pain on her skin and the worm will have emerged to lay her eggs in the water.
Chris - So the worm makes the person go into water effectively, and this causes the blister to rupture and the worm escapes.
Mark - Correct.
Chris - So how does another person then recapture that worm or get the parasite in that way?
Mark - The eggs will be ingested by a very small crustacean called a cyclops, it's a copepod, and when people drink unfiltered water they ingest the copepod. The eggs emerge when the copepod dies and they then mature into adult worms.
Chris - Is this something that we might be able to stop because these things are pretty common, you've got lots of people fishing and swimming in all this water in places like Africa, and it sounds like it's going to be a self-perpetuating cycle forever.
Mark - Well guinea worm is one of the few success stories we have against parasitic infections. From a prevalence of about three and a half million people infected just a few years ago, in 2004 the annual number was 16 000.
Chris - So that's a massive reduction isn't it.
Mark - It is, and it's because of the mode of transmission. It's rather easy to intercept by putting muslin cloths over basins and pots for example.
Chris - So education's everything.
Mark - Indeed.