Episode 162      21 min 02 sec
Worming their way: Parasites, their larvae, and your brain

Parasitologist Professor Marshall Lightowlers explains the risk to animal and human health posed by parasitic flatworms, and how even neurological disorders like epilepsy can result from exposure to tapeworm larvae. With host Dr Dyani Lewis.

"In many parts of the world, where people are poor and have very little education, those behavioural practices don't occur and are very difficult to change. So that we are looking to develop vaccines to help prevent the transmission of the parasites." -- Professor Marshall Lightowlers




           



Prof Marshall Lightowlers
Professor Marshall Lightowlers

Melbourne Laureate Professor Marshall Lightowlers is Principal Research Fellow with the National Health and Medical Research Council and Professor in the Department of Veterinary Science at The University of Melbourne.  Professor Lightowlers’ research career has focused on the immunology and molecular biology of taeniid cestode parasites. He was a member of a team of scientists which developed the first recombinant vaccine against a parasitic disease. Subsequently he has sought to development similar vaccines against infection with the larval stages of cestode parasites causing zoonotic infections in humans. This led to the development of highly effective, recombinant vaccines against cysticercosis caused by Taenia saginata and Taenia solium. He and his colleagues also produced a recombinant vaccine against infection with the parasite that causes hydatid disease. The effectiveness of these vaccines makes them unique in helminth parasitology and they provide valuable models for the development of vaccines against other eukaryotic parasites. Professor Lightowlers’ vaccines against Taenia solium and Echinococcus granulosus are undergoing further development and optimization in preparation for their practical use.  Application of the vaccines will be expected to reduce the transmission of these parasites and thereby reduce the number of new human cases of hydatid disease and neurocysticercosis.  Professor Lightowlers has served as President of the Australian Society for Parasitology and was awarded that society’s Bancroft-Mackerras Medal in recognition of his outstanding contribution to the Science of Parasitology.

Credits

Host: Dr Dyani Lewis
Producers: Kelvin Param, Eric van Bemmel
Audio Engineer: Gavin Nebauer
Voiceover: Dr Nerissa Hannink
Series Creators: Eric van Bemmel and Kelvin Param

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VOICEOVER 
Welcome to Up Close, the research talk show from the University of Melbourne, Australia.

DYANI LEWIS 
I’m Dyani Lewis. And thanks for joining us. When we think of epilepsy we don't often think of parasites, specifically intestinal worms as being the possible cause. But for people living in poor communities of Africa, Latin America and Asia parasitic tapeworms are the most common preventable cause of this debilitating neurological condition. Today we are joined by a pioneer in the field of molecular parasitology, Professor Marshall Lightowlers. In 1989 Professor Lightowlers and his team developed the first ever recombinant vaccine against the parasitic worm. Today he's here to tell us more about tapeworms, the potential for animal vaccines to combat these parasites and what this means up the food chain for human health. Professor Lightowlers is a Melbourne Laureate Professor at the School of Veterinary Science here at the University of Melbourne and a Principal Research Fellow with the National Health and Medical Research Council. Welcome to Up Close, Marshall.

MARSHALL LIGHTOWLERS 
Thank you, Dyani. 

DYANI LEWIS
Marshall, your work focuses on a number of different tapeworms species but I thought we could perhaps start with a quick description of what a tapeworm is and how it differs from some of the other worms that there are?

MARSHALL LIGHTOWLERS
Dyani, there are two principle groups of worms there are round worms and flat worms and tapeworms are one of the types of flat worms. They are of interest to us because some of them cause human disease and some of them cause problems in domestic livestock animals as well.

DYANI LEWIS 
So the main species of tapeworm that you work on is Taenia solium the pork tapeworm and this is worm that lives, as an adult within the intestines of humans. So why the name pork?

MARSHALL LIGHTOWLERS
This parasite, Dyani, in common with the other parasites in the same group has a life cycle that involves two different animals. One is a carnivore and the other is a prey species, so that this particular parasite that is a tapeworm in the small intestine of humans has its larval stages in the meat of infected pigs. The worm must circulate between the host that has the adult tapeworm and another that has the larval stage. It must go human to pig to human to pig in a cycle like that.

DYANI LEWIS
So the larval stage, what does that look like in the pig?

MARSHALL LIGHTOWLERS
It's a small maybe about 5 to 10 millimetre clear fluid filled bladder that would look to a non‑expert just like perhaps a piece of fat. You would eat it without any hesitation.

DYANI LEWIS
So it occurs in the meat of the pig that is then consumed by the human?

MARSHALL LIGHTOWLERS
That's correct, that's how humans get infected with the tapeworm.

DYANI LEWIS
Once inside the human intestine, how big do these worms get?

MARSHALL LIGHTOWLERS
Well as much as 10 metres in length. They're quite spectacular and beautiful things.

DYANI LEWIS
I imagine that causes a number of symptoms, does it?

MARSHALL LIGHTOWLERS
Remarkably it causes very little symptom at all So having a giant tapeworm in your small intestine does you very little harm directly. Tapeworms have a bad reputation because they are so spectacular when you see them but in actual fact most of the worms that cause, directly, very serious problems to human health are much smaller worms that don't look so spectacular. They don't seem to be so fearsome to people who might see them, whereas the poor old tapeworm because it is spectacular looking gets a much worse reputation.

DYANI LEWIS
And it hangs around in the intestine for how long, indefinitely, does it?

MARSHALL LIGHTOWLERS
Well at least years.

DYANI LEWIS
So then, from that point the pigs get infected, how does that happen?

MARSHALL LIGHTOWLERS
Well each time you go to the toilet the sexually reproducing tapeworm produces eggs and they come out with your faeces. Then pigs become infected by eating something that is contaminated with human faeces, or indeed as very commonly happens, pigs in areas where people are not using toilets are directly eating the human faeces. So they will seek them out in a circumstance like that if they are free-roaming pigs. Because human faeces to them are quite nutritious and so it's commonly direct eating of the faeces that results in the transmission of the parasite.

DYANI LEWIS
Okay, so for the parasite to complete its life cycle the pigs eat the eggs which are present in the human faeces and then the human beings eat the pork meat containing the cysts. But far more sinister are the effects of when humans ingest the eggs. What happens then?

MARSHALL LIGHTOWLERS
The life cycle involving the tapeworm in a human intestine and the larval stages in the pig causes neither the human nor the pig any particular problem. But there are really major human health problems occur when humans accidentally eat the eggs from human faeces. Now the larval stage that should grow in the muscles of a pig has the capacity to grow in a human. So humans can be the host for both the adult worm as well as the larval stage. In humans, regrettably, the larval stage has a propensity to grow in the brain and cause quite serious neurological disease. So that in your introduction you referred to epilepsy and that is one of the major symptoms of infection of the larval stages in the brains of humans.

DYANI LEWIS
So how quickly does that occur, as soon as someone is infected?

MARSHALL LIGHTOWLERS
What the symptoms are in fact depends very much on how many parasites are growing in your brain and just whereabouts they are in your brain. The parasite takes two or three months to mature from a very early larval stage into a mature potentially infective one. When they reach their mature size, they generally stop growing and so perhaps you might expect the symptoms to occur sometime after a few months after infection. But it's a very variable thing and symptoms are more likely to occur indeed if the parasites for one reason or another were to die in your brain. Because then you have a foreign body effectively which is in the order of perhaps up to a centimetre in diameter releasing a whole lot of foreign material causing inflammation. The inflammation can bring on symptoms, medical, clinical symptoms.

DYANI LEWIS
So is there treatment available for this type of infection?

MARSHALL LIGHTOWLERS
If you are unlucky enough to have these larval stages in your brain it is possible to have them killed using medical treatments, chemicals. But because of the possibility of producing inflammation after the parasites are killed by the chemicals, that really needs to be done, in a really first class medical setting. Because it is possible that the symptoms can be much worse or possibly even fatal following treatment. Whereas prior to treatment with the living parasites there may have been few symptoms or no symptoms. So yes it is possible to treat but it's a difficult and very specialist thing to do that.

DYANI LEWIS
So, Marshall, where in the world is the pork tapeworm found and how common is it?

MARSHALL LIGHTOWLERS
It's a problem really in countries where there are free-roaming pigs and where people don't use toilets. Remarkably that's quite a lot of the world and it tends to be very poor countries or very poor parts of countries. So many of the parts of Central America, North and South America, parts of Asia and many countries in Africa have the problem because those conditions are present.

DYANI LEWIS
What about in countries that perhaps don't eat pork for religious reasons?

MARSHALL LIGHTOWLERS
Well interestingly we do get transmission of the parasite at least from human with a tapeworm to human getting the larval stage in many countries including in the rich countries such as the United States. Because people who have tapeworms can go on holidays or migrate and take their tapeworm with them and unwittingly, accidentally contaminate, if they are working in the food industry, preparing your salad for lunch and they are not particularly careful with their hands, after they've been to the toilet. Then they can contaminate what you eat and you could get infected with the larval stages in circumstances where there is no actual transmission. I mean human to pig to human to pig really that only occurs where pigs get access to human faeces. That does to occur for example in the United States. But it is theoretically possible and it does happen from time to time that transmission from human to human occurs in any country.

DYANI LEWIS
Right, so no one is immune then?

MARSHALL LIGHTOWLERS
That's correct.
DYANI LEWIS
I'm Dyani Lewis, my guest today is Professor Marshall Lightowlers and we're talking about epilepsy and intestinal worms, here on Up Close coming to you from the University of Melbourne, Australia. In terms of preventing tapeworm infection it sounds like good food hygiene practices and ensuring that meat is properly cooked would go a long way to controlling tapeworm infection. But you're looking at vaccines, why is that?

MARSHALL LIGHTOWLERS
You're exactly correct that there are behavioural and animal husbandry practices that can completely prevent the transmission of this disease. But in many parts of the world, where people are poor and have very little education, those behavioural practices don't occur and are very difficult to change. So that we are looking to develop vaccines to help prevent the transmission of the parasites.

DYANI LEWIS
So what stage of the life cycle are you targeting with your vaccines?

MARSHALL LIGHTOWLERS
Dyani, if we step back a little and have a think about this group of infectious organisms, parasites belong to the same group of organisms that we do. They are very, very complicated, very genetically complex and very clever, genetically. The vast of majority of parasites are very poorly susceptible to our immune responses. We are unable to control them. So it's typical that infections with parasites can occur frequently. The can occur over and over and the infections are very long lasting. Now for this particular group of parasites, the parasite taenia solium, the one that's causing this infection in pigs and in humans it has a very brief period in its life cycle, in the early larval stage which is actually susceptible to attack by immune responses. So we've been able to target that very brief period in the long transmission life cycle of the parasite and to identify proteins that make that early larval stage susceptible to immune attack. Then to produce those in a laboratory using genetic engineering techniques and then successfully use those as vaccines.

DYANI LEWIS
So this is essentially vaccinating the pigs against the larval stage, why not just vaccinate humans?

MARSHALL LIGHTOWLERS
Well the vaccine that we've produced prevents infection with the larval stage and we could be very confident, in fact that it would work, if we were to use it directly in humans. Now the reason that we're not pursuing that is because it's extremely expensive to go through the clinical trialling and the other trialling that's necessary to produce any new human pharmaceutical. Because this particular infection is virtually entirely restricted to very poor countries and poor people in poor countries there is just not the financial support to support the very huge costs. I am literally talking hundreds of millions of dollars, to get up and license a new human product. Because the disease is transmitted through livestock animals, through pigs it means that if we were to use a successful vaccine in the pigs we can indirectly remove the source of infection for people. Because if pigs aren't infected, humans can't get tapeworms. If humans can't get tapeworms then humans can't transmit the larval stage to themselves or other humans. So we can vaccinate livestock and develop a new livestock vaccine much less expensively than we can a new human product and it's for that reason that we're targeting the vaccination at pigs.

DYANI LEWIS
Now a lot of vaccines are made from either dead or inactive organisms that they are designed to protect against. But you've said you've used genetic engineering. How has that worked?

MARSHALL LIGHTOWLERS
You're exactly correct that many vaccines are made using either killed organisms or extracts from organisms. But this parasite has a complex life cycle. We can't replicate it and grow it in the laboratory. Which means that it's absolutely impossible to obtain substantial quantities of the material on which we could base any kind of routine use product. So we had no choice at all but to use some other method for producing the proteins that we need to produce. The simple way to do it and the way that many proteins are produced nowadays for many purposes is to take the gene from the parasite that encodes the protein that we are interested in to put it into a harmless bacterium in the laboratory. The bacterium then acts as a little factory. It produces its own proteins but as well it produces this foreign protein. Then we take those bacteria and extract and purify the protein that we want and we end up with a pure non-living product which is fundamentally the same as the protein would have been had we produced it from the parasite. But we are able to grow these bacteria really in unlimited amounts, in industrial amounts and produce an industrial quality control product in that way.

DYANI LEWIS
Now taking vaccines into developing countries can be fraught with numerous logistical issues such as a lack of adequate cold storage for the vaccines. How have you addressed some of these issues?

MARSHALL LIGHTOWLERS
Well you're exactly right, Dyani, there are still enormous challenges ahead of us in order to get these vaccines used in the places that they're needed. Now this particular vaccine doesn't have a problem with requiring to be kept refrigerated. That's a particular problem for vaccines that rely on live organisms. They typically require a cold chain so that's not one of the problems that we face. But we certainly face other problems to do with getting any vaccination used in the environment that these are going to be needed. The environments in which we need to vaccinate the pigs are environments that are typically remote, very poor where the pigs have very little treatment for any diseases. Where they are typically not vaccinated against anything. Even if we were able to produce the vaccine at no cost whatsoever they would then need to be taken to where the pigs are so that the pigs could be immunised. The people generally have very poor animal handling facilities and are suspicious about injecting anything into their animals. These provide really quite great challenges to us. Taking what is a spectacularly successful vaccine in laboratory trials and in our initial field trials that we've done in various places now, to rolling it out in a way where we can reduce or eliminate transmission of the neurological disease in humans. But I believe that in many places we will be able to achieve that. It's going to require collaboration between ministries for agriculture and ministries for health in endemic countries and philanthropic agencies. Because the funding for it is very likely going to be needed from outside the countries that need to use the vaccines. I say that because the countries that have a big problem with this particular disease have even bigger problems with other diseases that spring immediately to mind. HIV, malaria, tuberculosis and a whole string of other very serious human disease problems so that this particular neurological disease isn't at the top of the list of any country. But now that we have a very effective vaccine we have the possibility of actually doing something to remove this as one of the burdens of these poor people. So I think for that reason, I'm hoping that it will be attractive to philanthropic agencies and we will be able to make quite a big difference, at least in many parts of the world where it’s a problem.

DYANI LEWIS
So eradication is possible then?

MARSHALL LIGHTOWLERS
It's certainly theoretically possible because the disease is only transmitted by humans with the adult tapeworms and pigs with the larval stage. That means that there is not a reservoir of infection in wildlife. Humans are easy to get and treat, you can treat humans to remove the tapeworm with a very inexpensive and effective and non-toxic drug. Now that we have something to attack the stage in the pig, that is the vaccine, we have the possibility of simultaneously attacking both stages I the life cycle. Yes it is certainly possible that we could look in the eventual future to its elimination from regions and theoretically we could eradicate it from the globe.

DYANI LEWIS
So given that these tapeworms predominantly affect poorer countries, where does the funding come from for this kind of vaccine development work?

MARSHALL LIGHTOWLERS
Dyani, we're very lucky to have had ongoing support from Australia's premier medial research funding body the National Health and Medical Research Council. We've also had very substantial research funding from a group called the Wellcome Trust, which is based in the United Kingdom. More recently through an organisation called the Global Alliance for Livestock Veterinary Medicines or it goes by the acronym GALVmed. We've had funding to scale up the pig vaccine from the Bill and Melinda Gates Foundation. We are very fortunate to have had this support, and really without it we would never have been able to achieve the successes that we have to date.

DYANI LEWIS
Well, Marshall, thank you for being our guest today on Up Close and telling us about tapeworms and vaccinating against them.

MARSHALL LIGHTOWLERS
Thank you, Dyani, and absolute pleasure to be with you.

DYANI LEWIS
That was Professor Marshall Lightowlers a Melbourne Laureate Professor from The School of Veterinary Science here at the University of Melbourne and a Principal Research Fellow with the National Health and Medical Research Council. Relevant links, a full transcript and more info on this episode can be found at our website at upclose.unimelb.edu.au. Up Close is a production of the University of Melbourne, Australia. This episode was recorded on 22 September 2011. Our producers were Kelvin Param and Eric van Bemmel, audio engineering by Gavin Nebauer. Up Close is created by Eric van Bemmel and Kelvin Param.  I’m Dyani Lewis, until next time, good bye.


VOICEOVER
You’ve been listening to Up Close. We're also on Twitter and Facebook. For more information visit upclose.unimelb.edu.au.  Copyright 2011 the University of Melbourne.


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