 Aloha, owingala kakou. I'm Kaui Lukas, host of Hawaii is My Main Land, kicking off Pohana Fridays at 3 p.m. on the bright side and off the grid with local issues. There's a certain yuck factor in today's discussion on rat lungworm disease, but since it can kill you and it's found in many places across the Hawaiian islands, hang in there. Dr. Robert Kaui of University of Hawaii Manoa's Pacific Biosciences Research Center is here to give us practical information to protect us from infection, because at this point, rat lungworm is a permanent resident. With the goal of arming you with good science without alarming you, here's Dr. Kaui. Hi, Rob. Hi, nice to be here. Two Kaui's. As opposed to the three robs that were in the elevator coming up here. A lot of redundancy, but that's a good thing, right? Yeah, sure. I heard you give testimony at the legislature, and it haunted me for days, and then I had to invite you to come on the show, because I just had to hear more. So thank you. Welcome. Glad to be here. When you were at the legislature and talking to the committee, I think it was the AG committee, was there's a lot that's been happening with rat lungworm disease. It's not new, right? No, it's not new. The first known cases in Hawaii were in 1960. But we have more of them now. We do, and they've been seemingly on the increase since around about the year 2000. Okay, so first, let's find out from you how this nasty actor works. Okay. I understand it's a complicated life cycle. Yes, and in fact, what's on the screen right now is an image of an adult female worm. And you can see the sort of red and white stripes going down it. And white is the animal's gut. Sorry, it's the animal's nervous system. The red is the animal's gut, which is full of blood. It's been feeding on blood. And this is about an inch and a third long, an adult worm. Okay. So yes, we need to talk a little bit about some basic biology first so that people understand how they can become infected, the routes by which they can become infected, and how to prevent infection. And the image that's on the screen right now, if you look down at the, around about four o'clock it says heart. Worms become adult, mate and lay eggs. They do this, and those eggs then are transported from the heart through the pulmonary artery. The heart of the rat. Of the rat. You see the image of the rat down there at four o'clock. So the eggs are transported by the circulatory system to, ultimately to the lungs. They hatch into first stage larvae. These worms go through five stages, four larval stages, and an adult stage. So they're first stage larvae in the lungs. These move up the trachea of the rat, the windpipe of the rat, and are swallowed and go down through the gut and out the rat's back end in the feces. Then a snail comes along, or a slug, and eats those feces, and thereby ingesting the first stage larvae that are in the feces. Those first stage larvae then develop into second and third stage larvae in the snail, and it's the third stage larvae, and only the third stage larvae that are infective to humans. So what happens then is, and indeed to rats, we're actually talking about rats right now, and we'll get on to the humans. I'm getting ahead of myself. So rat comes along and eats that snail that's now got third stage larvae in it. And those larvae go down its gut with the snail, and they penetrate the walls of the gut and get into the circulatory system. And from there, the circulatory system carries them ultimately to the brain. It takes about a day to get from the gut very quick, very quick to the brain. So these are still third stage larvae. In the brain, they develop through the fourth stage into the fifth stage, which we call the sub-adult stage. They stay in the brain for a while, gradually maturing. Then they leave the brain. Remember, this is in a rat. They leave the brain, and it's important that they leave the brain because they have to get back to the pulmonary artery and the heart in order to reproduce these newly developed adults. So that's what happens. And so they're now in the heart. They reproduce first stage larvae, and the cycle goes round and round again. And that's the natural way of things. That's how it works in the wild. And they don't kill the rat. They just keep going around and around the merry-go-round. There's some evidence that if the rat has a very heavy infection, so a large number of worms, that it can cause bronchial problems and so on. So breathing problems because they're not getting enough blood through the pulmonary artery to make everything work. But you're saying they can last a good long while these rats... A really, really serious infection can kill them, and it probably kills them by blocking the circulatory system in the pulmonary artery and the heart. But on the whole, if they've got a milder infection, they can shrug it off and carry on. And carry on, carrying on making feces, which are then eaten by the snails and the slugs. Exactly, and it goes round and round. Okay, all right, so we're at the third stage. Okay, so the way humans get infected is when the larvae are at the third stage, and you can see this in the image on the screen, it's at around about 10 o'clock. The snails have already eaten the feces of the rats that have first-stage larvae. The worms have developed to the third stage, just like they did, as I explained before, in the normal cycle. But if a person eats the snail, and I didn't eat that snail that's on the screen, it's a live snail. But if a person eats the snail with those third-stage larvae in it, then the same sort of thing happens. It goes down your gut into your circulatory system, ultimately ends up in your brain. And the problem is that when those worms are in your brain, they're trying to get out because they want to get back to the heart in order to breathe. But our brains are different from rat brains, believe it or not. Wow, a scientist said that. Well, it's true. And so our brains are different, and they can't find their way out. To put it simply. And so what happens is that ultimately they die in the brain. And as a result of first of all cruising around trying to find a way out and causing all sorts of neurological damage in the brain, destruction of nervous matter in the brain. After having done that, they die. And it turns out that when they die, it causes a huge immune reaction in your brain. And that is, some would argue, even more serious than the actual physical damage of the worms cruising around in your brain trying to find a way out. And so this is what causes rat lungworm disease. This is not a picture of a human brain. This is a picture of worms in a rat's brain. It's pretty horrible. Just try and imagine that in your own brain. Not at all nice. And so what happens is that because of all this neurological damage, you get a whole range of different symptoms that can range from in a very mild case with, say, only a few worms in your brain. And we don't know how many worms are required to cause mild symptoms, more serious symptoms, or ultimately death. But the mild symptoms might be just a serious headache. You also get tingling on your skin that goes from place to place because obviously the worms are cruising around in your head to different parts of your head. So influencing different parts of your nervous system. So lovely. You'll get shoulder aching. You'll have jerky reactions, perhaps. Sometimes people's eyes look in opposite directions. Wow. And we're getting more serious now. You might have bladder dysfunction. You might have gut dysfunction. Ultimately, in a really serious case with lots of worms in your brain, you might go into a coma. And this has happened here in Hawaii. And ultimately, you might die. And that has also happened in a few cases in Hawaii. So we don't know how many worms it requires to result in a serious case. Talk about time frame. Can we talk? Do you know enough to talk about that? Well, I can talk about a time frame in a rat. We can't dissect humans and figure out where they are in the human body as they cruise around. But in a rat, like I said, it takes about a day to get to the rat's brain. And then they sit in the brain for about four weeks, about a month. And then they come out and go down into the heart to reproduce. So about a month. And we can assume that they're in the human brain for quite some time. Maybe as much as a month before they ultimately die because they can't find their way out. But we don't know that for sure. All right. It seems to be a lot we don't know. But we'll get back to that. So the worms are in the brain. They're cruising along with these weird symptoms. But is there some way to test for them? Can you see them on an MRI scale? Not to my knowledge on an MRI. Caps? You know, I don't know. I'm not a physician. But I know that there are various ways that people have tried to develop to detect the presence of worms in a person. One involves DNA sequencing to see if they can pick up the DNA sequence of a worm. They're trying to do that in the blood. But of course, if the worms are not in the blood any longer, then maybe there's no remnant DNA left. The other way that they've looked at is immunoassays. So when you're infected with the worms, your immune reaction creates antibodies to the worms. And they've tried to pick up antibodies. Is there some success with that? I think that they do that primarily... I may be confused myself here, but they do have to do lumbar punctures, so spinal taps in order to get nervous tissue fluid because the worms have gone into your nervous system. And they can actually occasionally see a worm in the nervous tissue. But I think they use that primarily for the immune assay. I'm not sure about the details of that. Again, it's not my expertise. We have one minute before we go for a break. So what actually causes death in Hickman's? Serious nerve damage. Neurological damage. There was something about encephalitis and I was like, oh, maybe... Yeah, that's the nervous damage. The symptoms of encephalitis. Meningoencephalitis. So it's the meninges swelling is what it is of the brain. And that's another aspect of diagnosis, is detecting what are called eosinophils, which are certain kind of white blood cells in the spinal fluid. Now, the problem with that is the other causes of having eosinophil levels heightened in your spinal fluid. Okay, so we're going to take a little break and try to think of something besides worms and come back back. Aloha, I'm Bill Sharp, your host at Asia Review. Watch us every week, every Monday afternoon for exciting up-to-date information and analysis about contemporary affairs in Asia. Aloha, Kako. I'm Marsha Joyner and I'm inviting you to navigate the journey. We are discussing the end-of-life options and we would really love to have you every Wednesday morning at 11 a.m. right here. Aloha, my name is Joe Kent and I'm the Vice President of Research at the Grassroot Institute of Hawaii. The Grassroot Institute is a public policy think tank and we try to build a better economy in Hawaii and you can see us on the TV show Ehana Kako on the Think Tech Hawaii Broadcasting Network every Monday at 2 o'clock. We'll see you there and let's build a better Hawaii together. Aloha. Welcome back to Hawaii is my name. I'm Kaui Lucas and with me today to talk about lung worm disease is Dr. Robert Kaui of the Pacific Biosciences Research Center at UH Manoa. So he's just taken us through the icky life cycle that jumps from brains to hearts and yuck, yuck, yuck. But this is important. It's real. While you were testifying at the legislature Senator Joy Bonaventura, who's a senator from Hawaii Island said, oh, I have a friend who's fighting for his life in the ICU right now. So it's real. So let's talk about where it is. Do we know how many people have been affected in Hawaii? We don't know how many people have been infected because you can be infected with a very few worms and you can have some mild symptoms but you might not report that. You might just think I drank too much last night. I've got a really bad headache. Some people go to the emergency room with a really bad headache and the physician who may not be aware of rat lung-worm disease and many physicians are not in Hawaii. Okay, well that's a problem. Yeah, that's a problem. They might just diagnose it as a bad case of the flu and send the person away. So it's not reported. The cases that are reported are those in which the symptoms match rat lung-worm disease, the history of the patient's interaction with snails perhaps matches rat lung-worm disease. And then ultimately one of these diagnostic things like the heightened eosinophil level, you put all that together and it sort of means that you're 90% confident that this is rat lung-worm disease. So we've had I think around about probably up to about 100 definitively determined cases of rat lung-worm disease. And I think maybe at least one death that I am aware of maybe a couple more but certainly some very serious infections involving people being in comas for three months for instance. In one case that I know about. And permanent brain damage. And potentially permanent brain damage, yes. I read a little bit about that. So let's go to, well it doesn't seem likely that one would come across this really. Snails and rat poop. I mean how much of us hang out with those things, right? But it's here in Hawaii. And thank you for this map. I want you to talk about what's on it and then also what's not on it. Or what isn't obvious from looking at it. So the map shows, well let me back up. I and others in my lab have done surveys of snails and slugs across the Hawaiian islands since 2003. And this doesn't show all the sites. It shows sites where we've screened snails and slugs for rat lung-worm disease. For rat lung-worm, not the disease. For the actual presence of the worms. And we've done this by sequencing DNA. And what the map shows you, the red dots are where we've detected the rat lung-worm in snails and slugs. The yellow dots are where we've screened snails and slugs but have not found rat lung-worm. That does not mean that the rat lung-worm isn't in those areas or in that species of snail. So for instance lanai. We did not find rat lung-worm on lanai in snails and slugs. But there has been a case, a human case on lanai. So we don't know whether rat lung-worm is on lanai or not. But what we do know is where the red dots are on the screen, that that's where rat lung-worm is present. Okay. And there are some things that are, these places have in common? It seems that where rat lung-worm is present, there's higher levels of rainfall. That seems to be, of the factors that we've evaluated, rainfall level seems to be important. So for instance, this might at least partially explain why you've got a high incidence of rat lung-worm disease on the east side of the big island, which is where the vast majority, 90% of the human cases have been, despite the fact that the rat lung-worm is on... All the other islands, except lanai. Except lanai. As far as we know. So how many sites have you tested? I think we've done around 185 sites. That's not a lot. It's part of a bigger survey of over 800 sites. And we could go to some of the material from those other sites and screen those. This was the material that we had at the time and it was part of a student's master's thesis and she had to get finished. She couldn't spend ten years screening these things. Okay, so it sounds... I keep hearing that we don't know, we don't know. Why don't we know? Okay, so that's a question that I ask myself often. I've tried to get money from various federal agencies, the National Science Foundation, the National Institutes of Health, the USDA, Department of Agriculture. And with the exception of one small grant that allowed me to... that requested that I run a workshop to try to identify research priorities. And this is the outcome of that workshop. It's the proceedings of the workshop. And that's available online? Which is available online, yes. Okay, at your site? At my lab website. Okay, the Pacific Biosciences Research... Actually, my own personal lab's website. So it's called Kaui Lab. Oh, Kaui Lab. One word, Kaui Lab. It's about C-O-W-I-E, not K-A-U-I. So anyway, I think that the main reasons why the federal agencies are not willing to fund this and when we get the reviewers of these grant proposals back, the reviewers even say this. They say things like, well, how important is this disease? And in the greater scheme of things, compared to things like cancer, malaria, heart disease, it's of minor importance, particularly in the United States. On the mainland, there's only been a handful, one or two even cases in humans, because there is rat lungworm increasingly being found on the mainland in the southeast, Louisiana, Florida, those kinds of places. Warm and wet. And I think that this is the reason that the federal government is not, at this point anyway, willing to fund it. And what we hear is sort of like, it's an invasive species. Right. And like any invasive species, agencies, government agencies are loath to spend money until they know it's a problem. The problem then is that when it becomes a problem, it's too late because it's established and you can't eradicate it and you have to do sort of rear guard action. Okay, so you're going to help us stay safe. Right. Okay, so how do we do that? Okay, so you have to remember that the way you get infected is by eating those third stage larvae, which are in snails and slugs. So you can eat, and a snail or a slug has to be raw or at least under cooked. If you cook them really well, then it's okay because that cooking kills the worms inside them and you just get a bit more protein. So the thing is, and there have been cases where people do eat raw snails and in Hawaii, the first case in Australia, I think the first case in Brazil, there have all been guys often drunk. These guys, and they're often drunk, sit on a dare or for a bet. They say, I bet you wouldn't eat that snail that's crawling around here or eat that slug and I'll pay you 200 bucks. And of course the drunk guy does and gets seriously infected. The wages of stupidity. There's been one very serious case here. So does that mean that we don't have to be... No, no. So that's deliberately eating raw snails. Just don't do it. Don't do it. Why would you want to do it anyway? Really? But the other way you can get infected is inadvertently without realizing that you've eaten like a baby snail or slug in amongst your lettuce leaves. And so these can be maybe just an eighth of an inch long when they hatch out of their eggs and maybe a little bit translucent. So it's really difficult to see them in amongst your leafy greens. And so... All of these different things that we're seeing, they're all potential hosts. These are the hosts, the snail and slug hosts that we've shown to be able to carry rat lung worm in the Hawaiian islands. The ones that we didn't detect it in are not necessarily unable to host it. It's just that we didn't collect snails that had it. And you can see from this bar chart that some species are better than others at carrying the rat lung worm. So the big tall bar on the left of this graph is what we call the semi-slug on the big island. And this is heavily implicated in the human cases in the Pune district of the big island. The other ones, the next one, the second one, is the big black slug. That's in every yard. Less so than the big brown slug. There's two of these big slugs. There's a black one and a brown one. That's the black one. I've got it in my yard. I've also got the brown one. The brown one is further down towards the end, less infected than the black one, but nonetheless is able to carry rat lung worm. And so the different species, like snails and slugs, don't touch them unless you've got gloves. Stop your children playing with them because little kids particularly will put them in their mouths. That's something that people often ask, can you get rat lung disease from the slime? And there's some equivocal evidence for that in as much as people have looked for worms in slime of snails and slugs, but they've only found very, very small numbers. So my feeling is that the chances of getting infected just by the slime are much, much less than by eating a raw baby snail in amongst your lettuce leaves. So the key is to wash your lettuce. Wash your lettuce. And any other leafy greens or any other projects, and not just from the perspective of rat lung worm, but from the perspective of any other kinds of food-borne diseases and bacteria and whatever. In our last minute I remember from your presentation that they did a study that tried bleach and everything else to wash, but the effective thing was just tap water. Just tap water. And we've done experiments where we've tried to put snails and slugs into lettuce leaves, on lettuce leaves, and we've tried to wash them off with these various things. You don't want to just kill them in situ because then they'll release all their worms and those worms can survive for a very short space of time outside the snail in a damp, humid environment and you would just be eating worms. So you want to wash the snails off. That's the key. You don't need to kill them. Just wash them off. Regular tap water works just as well as bleach, vinegar or salt water, which are the things that we tested. Initially, we also tested a bunch of those commercially available products for washing produce. And again, tap water works just as well as anything. Thank you so much, Rob, for clearing up some of the slimy business for us. And we'll see you next week. Aloha. Thanks for having me. Much appreciated.