WEBVTT - Ep 129 Lymphatic Filariasis: Hiding in plain sight 0:00:00.320 --> 0:00:00.640 Rehab. 0:00:00.760 --> 0:00:04.280 Joshua runs a small business in Plateau State, Nigeria, selling 0:00:04.360 --> 0:00:07.080 rice and ground maize at the local market. She has 0:00:07.120 --> 0:00:11.000 a great smile, six bright children, a supportive husband, and 0:00:11.119 --> 0:00:15.040 she has lymphatic philariasis. I used to have fever attacks 0:00:15.080 --> 0:00:17.360 and for weeks I could not do anything, not even 0:00:17.400 --> 0:00:20.800 take care of my family. Rahab noticed the symptoms of 0:00:20.880 --> 0:00:24.640 lymphatic philoriasis or l F when she had her fourth child, 0:00:24.720 --> 0:00:27.000 and the progressive swelling of her legs sent her on 0:00:27.080 --> 0:00:30.800 a desperate search for treatment. The journey for relief brought 0:00:30.840 --> 0:00:35.000 none and depleted her family's finances. One man used a 0:00:35.080 --> 0:00:38.000 razor blade. He made cuts in my leg, then used 0:00:38.040 --> 0:00:41.000 the suction device. He told me he had removed something. 0:00:41.400 --> 0:00:43.920 But if he took something out, why was the leg 0:00:43.960 --> 0:00:48.519 getting bigger and bigger. As Perhabs deformity grew, her circle 0:00:48.560 --> 0:00:49.640 of friends shriveled. 0:00:50.240 --> 0:00:50.320 Some. 0:00:50.400 --> 0:00:52.880 One gave me new clothes to pass on to another woman, 0:00:53.200 --> 0:00:55.800 but she refused to collect them because they came through me. 0:00:56.520 --> 0:01:00.480 During that time, I cried a lot. You can't imagine 0:01:00.480 --> 0:01:03.400 how happy I am that my children and grandchildren will 0:01:03.400 --> 0:01:04.560 never have to go through this. 0:01:51.880 --> 0:01:55.080 Wow. Yeah, yes, awful. 0:01:55.240 --> 0:02:01.520 It's unbelievable, and it's still so prevalent. 0:02:01.720 --> 0:02:05.400 It is, and fortunately there are a lot of great 0:02:05.520 --> 0:02:09.400 organizations doing work on this, such as the Carter Center. 0:02:09.520 --> 0:02:13.600 So Rahab's story was featured in a video produced by 0:02:13.680 --> 0:02:19.040 the Carter Center titled Living with Complications from Lymphatic Philriasis, 0:02:19.280 --> 0:02:21.799 and we will post the link to this video as 0:02:21.840 --> 0:02:24.799 well as to the Carter Center's website on all the 0:02:24.800 --> 0:02:27.840 incredible work that they are doing to eliminate or at 0:02:27.919 --> 0:02:31.519 least reduce the burden of lymphatic hilariasis in many countries 0:02:31.639 --> 0:02:36.440 around the world. Yeah, yeah, Hi, I'm Aaron. 0:02:36.240 --> 0:02:38.760 Welsh and I'm Erin Alman Updike. 0:02:38.560 --> 0:02:41.520 And this is this podcast will Kill You, And today. 0:02:41.360 --> 0:02:43.160 We're talking about lymphatic philiasis. 0:02:44.040 --> 0:02:46.840 This has been on our list for a very long time. 0:02:47.919 --> 0:02:50.560 It's kind of amazing that we haven't covered it sooner. 0:02:50.680 --> 0:02:56.640 It's one of the most prevalent and debilitating neglected tropical diseases. 0:02:57.520 --> 0:02:59.720 And I you know, I thought I knew a good 0:02:59.760 --> 0:03:03.040 am out about this disease from like public health classes 0:03:03.120 --> 0:03:10.160 and whatnot, but I was wrong. Same same, yeah, yeah, 0:03:10.919 --> 0:03:13.960 But before we get into all of the things that 0:03:14.040 --> 0:03:16.560 we now know about lymphatic philoriasis. 0:03:17.520 --> 0:03:19.040 Is it quarantiny time? 0:03:19.560 --> 0:03:22.320 It is? What are we drinking this week? 0:03:22.440 --> 0:03:25.520 We're drinking it's a small worm after all. 0:03:26.680 --> 0:03:32.040 Continuing with the worm world puns were our Quarantini titles, 0:03:33.360 --> 0:03:35.680 there's really like, it's a deep well, so it is, 0:03:35.880 --> 0:03:38.840 it's good and what is in It's a small worm 0:03:38.880 --> 0:03:39.400 after all. 0:03:39.520 --> 0:03:42.120 It's a lovely little hard cider bev with you know, 0:03:42.200 --> 0:03:46.800 heart cider and some ginger beer and lemon juice and 0:03:46.840 --> 0:03:49.720 some apple jack in there as well. Yeah, and we'll 0:03:49.760 --> 0:03:52.600 post the full recipe for that quarantini and the non 0:03:52.680 --> 0:03:56.200 alcoholic and equally delicious plusy Burta on our website This 0:03:56.240 --> 0:03:59.840 podcast will Kill You dot com and our social media. 0:03:59.080 --> 0:04:01.880 On our website This Podcast will Kill You dot Com. 0:04:01.960 --> 0:04:04.600 You can find all sorts of things. I have actually 0:04:04.680 --> 0:04:06.320 the website open in front of me. 0:04:06.840 --> 0:04:07.720 I love it when you do. 0:04:08.040 --> 0:04:11.760 If we have got links to bookshop dot org, affiliate account, 0:04:11.760 --> 0:04:15.000 our Goodreads list, merch and we've got some new merch 0:04:15.080 --> 0:04:18.080 coming for you this winter, which is pretty exciting, so 0:04:18.279 --> 0:04:22.200 keep an eye out. We've got links to Patreon. We've 0:04:22.240 --> 0:04:24.400 got a form for your first hand account if you 0:04:24.400 --> 0:04:26.760 want to submit a first hand account. We've got transcripts, 0:04:26.800 --> 0:04:28.720 and we've got the sources to each and every one 0:04:28.760 --> 0:04:32.200 of our episodes, plus some more hidden Easter eggs that 0:04:32.240 --> 0:04:34.000 you might find on the website. 0:04:34.080 --> 0:04:39.640 Ooh, easter eggs, Aaron, Yeah, all right, Well, shall we 0:04:39.800 --> 0:04:43.880 get into the biology of lymphatic philaiasis. 0:04:44.320 --> 0:04:47.960 We shall. We'll take a quick break and then dive in. 0:05:12.480 --> 0:05:12.600 So. 0:05:12.920 --> 0:05:18.240 Lymphatic phileariasis is the disease that is caused by three 0:05:18.480 --> 0:05:23.800 different but closely related nematode worms, specifically a type of 0:05:23.800 --> 0:05:28.039 worms called filarial worms, which are like a whole superfamily 0:05:28.200 --> 0:05:34.200 of these little round worms, small worms that are entirely parasitic. 0:05:34.360 --> 0:05:38.040 So almost all of these filarial worms infect mammals and 0:05:38.120 --> 0:05:41.800 some infect birds or reptiles. Apparently they do not infect 0:05:41.839 --> 0:05:46.920 fish that we know of that we know of, good 0:05:46.920 --> 0:05:51.479 one erin and generally they have a pretty complex life 0:05:51.480 --> 0:05:55.920 cycle with an arthropod intermediate host, so at minimum we're 0:05:55.920 --> 0:06:00.839 talking about a two host life cycle, pretty classic for parasites. 0:06:02.000 --> 0:06:04.840 And the worms that we'll talk about today are all 0:06:04.880 --> 0:06:08.599 in the family Onco Circudae, which we've already talked about 0:06:08.760 --> 0:06:12.760 one other time in our River Blindness episode. Anco circavolvulus. 0:06:13.720 --> 0:06:16.880 But today we're talking about three others. We're talking about 0:06:17.040 --> 0:06:23.840 Wuchereria bancrofty, Brugia or Brugia malai, and Brugia timori. 0:06:24.680 --> 0:06:29.800 Just side note here, we both did a lot of 0:06:29.839 --> 0:06:35.159 digging to try to find the correct pronunciation for these worms. 0:06:35.000 --> 0:06:36.719 Could not come to a solid conclusion. 0:06:36.760 --> 0:06:40.960 There is no consensus. It appears any YouTube video, you're 0:06:41.279 --> 0:06:44.880 bound to find a million different pronunciations. So this is 0:06:44.920 --> 0:06:45.760 what we're going with. 0:06:46.080 --> 0:06:52.680 We tried really hard, we did, but it's these three worms, 0:06:52.760 --> 0:06:58.400 and even more specifically, ninety percent of lymphatic phileariasis infections 0:06:58.440 --> 0:07:04.679 are caused by bancrotan phileiasis, which is caused by Woocheria bancrofty. 0:07:06.200 --> 0:07:10.840 I think that I suspect that most listeners of TPWKY 0:07:11.160 --> 0:07:15.200 are relatively familiar with the life cycle of Arthur bodborne 0:07:15.280 --> 0:07:19.040 parasites by this point. But we'll go over it because 0:07:19.080 --> 0:07:22.360 that's what we do here, and in this case, we'll 0:07:22.440 --> 0:07:26.920 start with the L three larvae. So the third stage 0:07:27.240 --> 0:07:33.440 larvae are what mosquitoes will spit under the skin as 0:07:33.480 --> 0:07:36.440 they bite us in order to infect a human. Is 0:07:36.480 --> 0:07:40.280 spit the technical term for this Yeah, that's the official 0:07:41.160 --> 0:07:47.120 scientific term for a mosquito bite. They will inject from 0:07:47.200 --> 0:07:50.400 their salivary glands the l three larvae during a bite. 0:07:50.680 --> 0:07:53.040 Yeah, that sounds like spit to me, so, yeah, exactly. 0:07:54.320 --> 0:07:57.200 And by the way, you may ask Aaron, what species 0:07:57.240 --> 0:07:59.040 of mosquito are we talking about? 0:07:59.280 --> 0:08:00.440 Is it lats of them? 0:08:00.720 --> 0:08:04.200 It is all all of them almost, it seems. 0:08:04.240 --> 0:08:07.160 That's really amazing. 0:08:07.600 --> 0:08:11.200 Yeah, so this is a parasite or these are parasites 0:08:11.320 --> 0:08:15.720 rather that are found across the globe, especially in the tropics. 0:08:15.800 --> 0:08:19.760 Throughout the tropics, and so in different parts of the world. Unsurprisingly, 0:08:19.840 --> 0:08:24.080 we have different vectors that are predominant in Africa. Across 0:08:24.120 --> 0:08:28.240 most of Africa, the most common vector are anophilies mosquitoes 0:08:28.400 --> 0:08:32.120 of a few different species. In the Americas, it tends 0:08:32.160 --> 0:08:37.520 to be qlex Quinca fasciatis, but eighties mosquitoes and Mansonia 0:08:37.520 --> 0:08:41.160 mosquitoes can also transmit the infection, especially in the Pacific 0:08:41.280 --> 0:08:45.640 in Asia and the Pacific, and these are predominantly Brugia species. 0:08:46.480 --> 0:08:49.400 These are also entire genera of mosquito. It's not just 0:08:49.440 --> 0:08:51.480 like one or two species that we're talking about here. 0:08:51.720 --> 0:08:54.440 Yeah, okay, so tell me what's going on inside of 0:08:54.440 --> 0:08:58.080 these mosquitoes that these parasites are somehow able to do 0:08:58.600 --> 0:08:59.760 everything to all of them. 0:09:00.240 --> 0:09:05.320 Oh, such a good question, Arin, I don't know. So 0:09:05.920 --> 0:09:09.120 these are parasites, and we'll talk about this in how 0:09:09.160 --> 0:09:14.880 they affect humans especially, but they are very well adapted 0:09:15.360 --> 0:09:19.520 to their hosts. They do a lot to modulate our 0:09:19.800 --> 0:09:24.040 immune system in a way that creates tolerance so that 0:09:24.120 --> 0:09:28.880 they can persist for their lifetime. So I imagine, though 0:09:28.920 --> 0:09:31.760 I don't know the details of how they do this 0:09:32.080 --> 0:09:35.040 in all of these various mosquito species as well, it 0:09:35.160 --> 0:09:38.920 is impressive that a single parasite can do so in 0:09:39.040 --> 0:09:41.200 so many different species of mosquito. 0:09:41.679 --> 0:09:45.000 Yeah, I feel like that's sort of the opposite. And 0:09:45.040 --> 0:09:47.640 maybe it's not. Maybe that's just like human bias or 0:09:47.760 --> 0:09:50.640 human infection bias, but that we've seen with a lot 0:09:50.679 --> 0:09:54.640 of vector born diseases where the parasite or pathogen is 0:09:54.679 --> 0:09:59.440 super loyal to their vector species but not necessarily to 0:09:59.559 --> 0:10:02.920 their hope, like they can infect a wide range just 0:10:03.080 --> 0:10:05.640 seems like a gambling like where do you put your 0:10:05.840 --> 0:10:07.720 like which basket do you put your eggs in? 0:10:08.280 --> 0:10:12.280 Yeah, and this really is the opposite because especially Wuscheria 0:10:12.679 --> 0:10:18.800 bancrofty is a really human specific disease. It can infect 0:10:18.880 --> 0:10:22.040 other animals, but in general it's not found in other 0:10:22.120 --> 0:10:26.240 animal species, and so it's almost like the opposite where 0:10:26.280 --> 0:10:31.800 this parasite has specialized on its primary host and is 0:10:31.880 --> 0:10:37.120 a generalist when it comes to the vector that transmits it. Question, okay, 0:10:37.920 --> 0:10:40.679 I love that we haven't even started. I'm like, you've 0:10:40.720 --> 0:10:42.520 got a larvae under your skin. Nuts. As far as 0:10:42.520 --> 0:10:43.880 we've gotten this is. 0:10:43.840 --> 0:10:45.559 An important part of the process. 0:10:45.640 --> 0:10:46.199 I love it. 0:10:47.520 --> 0:10:53.000 Do we know whether or not these parasites have detrimental 0:10:53.080 --> 0:10:56.439 effects on their mosquito hosts? 0:10:56.480 --> 0:10:59.320 Such a good question. I don't Okay, I don't know. 0:10:59.320 --> 0:11:02.720 I didn't specific look for that information, so I don't 0:11:02.760 --> 0:11:06.840 know if that information is known. A lot of other 0:11:07.679 --> 0:11:11.240 pathogens we know do have detrimental or at least some 0:11:11.360 --> 0:11:14.760 negative effect on the mosquitoes or arthropods that transmit them. 0:11:15.120 --> 0:11:18.160 I don't know. In the case of the parasites that 0:11:18.200 --> 0:11:21.199 coslymphatic philoriasis, I can tell you that when it comes 0:11:21.240 --> 0:11:26.000 to the development within a mosquito, these worms have to 0:11:26.160 --> 0:11:30.520 molt twice within the mosquito host, and it's a process 0:11:30.559 --> 0:11:33.600 that takes between ten and twelve days or maybe even 0:11:33.679 --> 0:11:37.520 up to two weeks per some papers, before they are 0:11:37.600 --> 0:11:41.439 then able to be transmitted to another host. So there 0:11:41.520 --> 0:11:44.760 is certainly time in there to exert kind of a 0:11:44.800 --> 0:11:47.480 selective pressure on that mosquito, and a mosquito has to 0:11:47.559 --> 0:11:50.800 survive for at least those ten to twelve days in 0:11:50.880 --> 0:11:52.600 order to be able to transmit the infection. 0:11:52.920 --> 0:11:54.240 Okay, yeah, that makes sense. 0:11:54.480 --> 0:12:00.120 Yeah, okay, So back to these L three larvae. They 0:12:00.200 --> 0:12:02.760 developed twice in the mosquito, and now they are spit 0:12:03.120 --> 0:12:09.240 into our skin. These tiny little larvae enter our lymphatics 0:12:09.280 --> 0:12:12.640 and swim their way towards our lymph nodes, and that 0:12:13.080 --> 0:12:17.160 is where they live. They molt into L four larvae 0:12:17.240 --> 0:12:21.000 and then into adults in a process that takes six 0:12:21.120 --> 0:12:25.160 to twelve months long standing infection. 0:12:25.520 --> 0:12:27.320 It's so long. 0:12:27.920 --> 0:12:32.160 Oh just wait, it gets longer. The adult female will 0:12:32.200 --> 0:12:38.160 then mate and then start releasing live young, and these 0:12:38.240 --> 0:12:44.040 young are called microfilaria, and they release them into the lymphatics. 0:12:44.080 --> 0:12:48.360 They can swim out of the lymphatics and into our bloodstream. 0:12:48.720 --> 0:12:53.040 Now erin, you may ask, how many microfilaria are we 0:12:53.120 --> 0:12:56.320 talking about that this adult female worm is releasing. 0:12:56.040 --> 0:12:57.680 That's definitely a question I would ask. 0:12:57.920 --> 0:13:02.400 Well, let me tell you. These adult worms live inside 0:13:02.400 --> 0:13:08.200 of us for up to seven to eight years after 0:13:08.360 --> 0:13:11.880 they become adult worms, and different papers have slightly different estimates, 0:13:11.880 --> 0:13:14.079 like four to six or five to eight. In any case, 0:13:14.440 --> 0:13:20.280 a number of years, and they are releasing ten thousand 0:13:20.760 --> 0:13:28.200 microfilaria wait for it, per day. What that is millions 0:13:28.440 --> 0:13:31.360 upon millions of microflaria over their lifetime. 0:13:32.120 --> 0:13:36.320 That is shocking. 0:13:36.960 --> 0:13:40.360 And then it gets more shocking. The adult worms are 0:13:40.400 --> 0:13:43.480 living inside of our lymphatic system. And we'll talk in 0:13:43.520 --> 0:13:45.880 a lot more detail about our lymphatic system. Don't worry, 0:13:47.000 --> 0:13:52.440 but these microfilaria predominantly travel to our blood vessels, and 0:13:52.520 --> 0:13:56.360 during the daytime preferentially hang out in our larger blood vessels, 0:13:57.320 --> 0:14:02.760 and then at night, when mosquitoes are most active, they 0:14:02.920 --> 0:14:06.240 travel to surface blood vessels so that mosquitoes can more 0:14:06.280 --> 0:14:09.679 efficiently pick them up in their blood meals and then 0:14:09.760 --> 0:14:11.599 go on to transmit them eventually. 0:14:12.280 --> 0:14:17.280 I mean, we've come across parasites that do this, like malaria, 0:14:18.080 --> 0:14:24.720 but it's still every single time is horrifying and fascinating, and. 0:14:24.600 --> 0:14:28.040 It's even more fascinating to me in the context of 0:14:28.120 --> 0:14:31.120 how many different species of mosquito can carry this parasite, 0:14:31.120 --> 0:14:35.800 because we do actually see different circadian cycles in these 0:14:35.880 --> 0:14:39.840 species of filarial worm depending on the part of the 0:14:39.880 --> 0:14:42.840 world that you're looking at and the mosquito species that 0:14:42.920 --> 0:14:46.440 is most commonly transmitting it in that region. So, for example, 0:14:46.520 --> 0:14:50.240 in the Pacific Islands, where they're transmitted by mosquitoes that 0:14:50.280 --> 0:14:54.360 are more diurnal, you see the microfilaria out in the 0:14:54.360 --> 0:14:57.080 surface blood vessels more during the day than at night. 0:14:57.360 --> 0:15:02.760 Like they're just so well adapted. It's incredible. 0:15:03.160 --> 0:15:07.560 That is really interesting, and I wonder how we could 0:15:07.600 --> 0:15:11.239 trace sort of spread or like how quickly that diurnal 0:15:11.360 --> 0:15:15.560 pattern evolves to match the local mosquito host, because like 0:15:15.600 --> 0:15:18.680 what happens if a new mosquito host, you know, comes 0:15:18.680 --> 0:15:23.080 in and is now suddenly the predominant mosquito host and 0:15:23.120 --> 0:15:25.480 can also transmit philariasis and. 0:15:27.200 --> 0:15:32.680 Yeah, yeah, oh, I know. It's it's so much so 0:15:32.800 --> 0:15:38.360 that is the transmission cycle of this parasite, of these parasites. 0:15:39.560 --> 0:15:43.280 So what does this disease, lymphatic philariasis actually look like. 0:15:44.720 --> 0:15:49.680 It turns out that, thankfully, most people who are infected 0:15:49.800 --> 0:15:53.800 are asymptomatic it's about one third of people who are 0:15:53.840 --> 0:15:58.480 infected who end up having clinical disease, actual symptoms of 0:15:58.520 --> 0:16:04.760 this disease. But even when people are asymptomatic, they generally 0:16:04.800 --> 0:16:09.960 still have some degree of damage to the lymphatic system, 0:16:10.560 --> 0:16:14.880 and this damage is progressive. And so the predominant symptom 0:16:15.560 --> 0:16:21.280 of lymphatic philariasis is lymphidema, swelling in a limb or 0:16:21.320 --> 0:16:25.200 in a body part due to disruption of the lymph system. 0:16:27.080 --> 0:16:33.160 And this swelling, this lymphidema lends itself to secondary infections. 0:16:34.480 --> 0:16:37.080 Really really easy to get a secondary infection when you 0:16:37.160 --> 0:16:39.600 have so much stasis of fluid. 0:16:40.480 --> 0:16:43.520 So why does that, like how does that happen? And 0:16:43.560 --> 0:16:45.880 maybe that's maybe my question is just like how does 0:16:45.920 --> 0:16:48.040 the lymph system work? What does it do? 0:16:49.800 --> 0:16:51.160 Let me get into that and then I can talk 0:16:51.160 --> 0:16:53.040 a little bit more about like what those symptoms end 0:16:53.160 --> 0:16:56.800 up looking like. Okay, yeah, So the primary cause of 0:16:56.840 --> 0:17:01.240 disease is the blockage of our lymphatic drink. So we've 0:17:01.280 --> 0:17:03.720 only talked in very brief about our lymph system on 0:17:03.760 --> 0:17:09.000 this podcast, But what our lymphatic system is is a 0:17:09.080 --> 0:17:14.000 system of tubes, vessels, and clusters of nodes. 0:17:14.119 --> 0:17:14.760 Lymph nodes. 0:17:15.080 --> 0:17:18.960 So it's very similar to our blood vessels in that 0:17:19.040 --> 0:17:22.240 what our lymph system is doing is carrying fluid from 0:17:22.240 --> 0:17:25.320 place to place in our body. Our blood vessels are 0:17:25.359 --> 0:17:30.800 carrying blood, and our lymphatic vessels are carrying lymphatic fluid. 0:17:31.680 --> 0:17:35.760 What is lymphatic fluid, it's basically just all the fluid 0:17:35.800 --> 0:17:39.800 in our body that isn't blood. So this means anything 0:17:39.920 --> 0:17:43.959 that either extravasates comes out of our blood vessels and 0:17:44.160 --> 0:17:49.800 into the extracellular space. Any cells that kind of burst 0:17:49.840 --> 0:17:54.360 open and release all of their lovely liquidy juices, that's 0:17:54.400 --> 0:17:57.760 going to become fluid in the extracellular space. So it's 0:17:58.000 --> 0:18:03.119 fluid and large molecules like proteins, et cetera, hanging out 0:18:03.160 --> 0:18:07.080 in all of the space between our cells. This fluid 0:18:07.480 --> 0:18:14.560 eventually is absorbed into the lymphatic system and carried through 0:18:14.640 --> 0:18:19.560 these tubes, through these lymphatic vessels into our lymph nodes. 0:18:19.640 --> 0:18:23.439 It kind of drains into our lymph nodes. Our lymph 0:18:23.480 --> 0:18:27.120 nodes are these areas where a whole horde of our 0:18:27.200 --> 0:18:32.719 immune cells, especially our white blood cells, hangout. Because the 0:18:32.760 --> 0:18:37.200 fluid that's traveling through our lymph it has antigens in it, 0:18:37.200 --> 0:18:39.520 it has pathogens in it, it has just a bunch 0:18:39.600 --> 0:18:42.359 of junk. And so what our lymph nodes are doing 0:18:42.440 --> 0:18:46.239 are essentially cleaning it all up, filtering out all of 0:18:46.320 --> 0:18:49.719 the junk in this fluid, and then eventually running that 0:18:49.760 --> 0:18:52.520 fluid from our lymph nodes through our spleen which is 0:18:52.560 --> 0:18:55.440 like not really a giant lymph node, but kind of 0:18:55.480 --> 0:18:58.000 like a giant lymph node in a way, and then 0:18:58.080 --> 0:19:01.679 sending that fluid eventually back into our vascular system. So 0:19:01.760 --> 0:19:04.320 putting that fluid, once it's all cleaned up, back into 0:19:04.320 --> 0:19:07.320 our blood vessels. Does that make sense what our lymph 0:19:07.359 --> 0:19:08.320 system is and does? 0:19:08.600 --> 0:19:12.320 Yeah, like extra plumbing, non blood plumbing. 0:19:12.600 --> 0:19:14.960 Yeah, extra plumbing. That's a really it's a really good 0:19:14.960 --> 0:19:18.600 way of looking at it. Okay, So then lymphatic philoriasis, 0:19:19.200 --> 0:19:23.719 how do we get here? In lymphatic philriiasis, the adult 0:19:24.000 --> 0:19:29.560 worms are living inside of our lymph system, inside of 0:19:29.600 --> 0:19:34.600 these vessels and near our lymph nodes. And they're not 0:19:34.720 --> 0:19:39.040 just passively hanging out there. They are, like I said, 0:19:39.240 --> 0:19:44.560 making millions, tens of thousands of eggs per day for years. 0:19:45.800 --> 0:19:50.480 The adult worms live in these little nests. They make 0:19:50.480 --> 0:19:54.840 these little nests and because they need to exist in 0:19:54.920 --> 0:19:59.399 a space that is like our lymph node's job is 0:19:59.440 --> 0:20:03.760 to clean out pathogens, right, That's our immune system's literal 0:20:03.800 --> 0:20:07.280 only job is to prevent things like worms from living 0:20:07.320 --> 0:20:13.120 inside of us. So these worms are actively secreting compounds 0:20:13.200 --> 0:20:18.159 to modulate our immune system's response to them existing inside 0:20:18.200 --> 0:20:18.480 of us. 0:20:18.760 --> 0:20:21.399 Like, what better place to do that, It's just hiding 0:20:21.440 --> 0:20:22.280 in plain sight. 0:20:22.440 --> 0:20:26.879 Exactly exactly, So it just so happens that these worms 0:20:27.240 --> 0:20:31.840 is secreate all of these compounds that end up favoring 0:20:31.920 --> 0:20:36.199 an anti inflammatory immune response. So what they do is 0:20:36.359 --> 0:20:41.920 suppress the T cells that are pro inflammatory, and they 0:20:42.040 --> 0:20:49.159 upregulate our anti inflammatory response. So this overall suppression of 0:20:49.280 --> 0:20:52.880 inflammation is what allows these worms to persist inside us 0:20:52.920 --> 0:20:57.520 for so long. They create this condition of immunotolerance, and 0:20:57.560 --> 0:21:01.400 that is why that many people with this infection for 0:21:01.480 --> 0:21:05.920 many years might have no clinical signs or symptoms. However, 0:21:06.400 --> 0:21:09.040 that doesn't mean that there's not some degree of inflammation 0:21:09.200 --> 0:21:12.960 happening within these lymphatics because of this infection, because of 0:21:12.960 --> 0:21:18.400 these worms, because they are producing these microfilaria that are 0:21:18.720 --> 0:21:23.119 bursting out of our lymphatics, running rampant and getting into 0:21:23.160 --> 0:21:26.440 our blood vessels. And so what we see is that 0:21:26.520 --> 0:21:29.800 even in people who have subclinical disease, that is, they 0:21:29.800 --> 0:21:34.040 don't have any symptoms of lymphatic philariasis, if you look 0:21:34.160 --> 0:21:37.199 inside of their lymphatics, they do still have some degree 0:21:37.240 --> 0:21:42.280 of inflammation in the lymph system, and over time, eventually 0:21:43.000 --> 0:21:46.560 people are at increased risk for overt disease. So the 0:21:46.680 --> 0:21:49.600 question that you asked is like, what triggers this, right, 0:21:50.800 --> 0:21:55.520 And while we don't fully know as usual, it's thought 0:21:55.560 --> 0:22:00.360 that it's related to the frequency and intensity of our 0:22:00.600 --> 0:22:06.359 eventual immune response to these worms, specifically the response to 0:22:06.400 --> 0:22:08.440 these worms as they die. 0:22:09.640 --> 0:22:13.000 Okay, and these are the adult worms or the microfilaria, 0:22:13.040 --> 0:22:13.919 the adult worms. 0:22:14.000 --> 0:22:18.280 Yeah, as these adult worms die, it causes an increase 0:22:18.320 --> 0:22:20.800 in inflammation. If you think about it, If they're actively 0:22:20.840 --> 0:22:24.640 secreting stuff to reduce inflammation and then they die, now 0:22:24.640 --> 0:22:28.400 they're not secreting those anti inflammatory compounds, right, So now 0:22:28.440 --> 0:22:32.159 you have an increase in inflammation. That increase in inflammation 0:22:32.520 --> 0:22:36.840 causes lymphangitis, which just means like swelling inflammation in your 0:22:36.880 --> 0:22:41.280 lymph system, lymphatinitis, which is inflammation specifically in like the 0:22:41.440 --> 0:22:45.679 lymph nodes themselves, okay, and then that is going to 0:22:45.720 --> 0:22:49.280 cause activation of our immune response. And we've talked a 0:22:49.280 --> 0:22:53.200 lot on this podcast about that like inflammatory cascade, where 0:22:53.520 --> 0:22:57.400 once you have inflammation, you're going to have more swelling. 0:22:57.680 --> 0:23:01.200 You're going to have this positive feedback loop that continues 0:23:01.240 --> 0:23:05.880 to upregulate these inflammatory pathways, which leads to more swelling 0:23:06.000 --> 0:23:10.399 and more swelling and more inflammation and importantly, more pain. 0:23:10.560 --> 0:23:15.040 This is a very painful process, and the frequency and 0:23:15.080 --> 0:23:18.960 severity of these attacks can then lead to chronic changes 0:23:19.320 --> 0:23:24.800 over time. Another factor that's involved in the development of 0:23:24.840 --> 0:23:31.520 this like symptomatic disease is a particular bacterial endosymbiant and 0:23:31.600 --> 0:23:34.240 longtime friend of the pod, h Wilbakia. 0:23:35.160 --> 0:23:37.520 Friend might be a generous term, but yes. 0:23:37.840 --> 0:23:39.840 I know, but I heard you say that on our 0:23:39.920 --> 0:23:42.199 last episode and I loved it so much. It was 0:23:42.200 --> 0:23:45.080 about cook, but I really wanted to say it again 0:23:45.119 --> 0:23:46.280 because I got a kick out of it. 0:23:46.440 --> 0:23:46.959 I love it. 0:23:48.200 --> 0:23:53.400 So These particular little endosymbiotic bacteria live inside of these 0:23:53.480 --> 0:23:59.040 tiny worms, and while the worms themselves are secreting anti 0:23:59.119 --> 0:24:05.639 inflammatory compounds, Walbakia happens to induce our innate immune system 0:24:06.200 --> 0:24:12.160 enormously and stimulate inflammatory pathways. They're like all inflammation. 0:24:11.920 --> 0:24:14.600 And this is again once the adult worm has died, 0:24:14.760 --> 0:24:16.840 or is this while the adult worm is living. These 0:24:16.920 --> 0:24:19.240 wolbachia are secreting these. 0:24:19.320 --> 0:24:22.480 Potentially both, but I think the thought is that a 0:24:22.520 --> 0:24:25.320 lot of it might be on death or like release 0:24:25.359 --> 0:24:29.920 of these wolbachia. So exposure to these likely also plays 0:24:29.960 --> 0:24:33.920 a role in the development of this lymphandritis, this inflammatory 0:24:33.960 --> 0:24:36.000 lymph system, and eventual lymphedema. 0:24:36.480 --> 0:24:39.200 So we talked about this with alco psychiasis. The Wollbacchia 0:24:39.280 --> 0:24:41.600 did the same thing, then, I yeah. 0:24:41.480 --> 0:24:44.720 Right, yeah, yeah, wobochia. Man. 0:24:45.040 --> 0:24:45.720 Yeah. 0:24:45.800 --> 0:24:50.280 Now, the other and possibly most important component of the 0:24:50.320 --> 0:24:54.520 progression of this disease is how open it leaves people 0:24:54.560 --> 0:25:00.480 to secondary infections, both because of the suppressive effec effects 0:25:00.640 --> 0:25:05.439 of this immune modulation, right, suppressing our immune systems so 0:25:05.480 --> 0:25:08.600 that we tolerate these worms makes people more susceptible to 0:25:08.680 --> 0:25:14.399 other pathogens like malaria or tuberculosis, but also because the 0:25:14.560 --> 0:25:18.040 damage that's happening to the lymph system and the eventual 0:25:18.119 --> 0:25:23.840 development of swelling of this lymphidema, this fluid stasis leads 0:25:23.920 --> 0:25:29.920 to secondary bacterial infections, and that process where you have 0:25:30.440 --> 0:25:35.040 fluid stasis, things not draining, and then secondary infections is 0:25:35.320 --> 0:25:39.119 literally how so many infections in our bodies happen, Like 0:25:39.520 --> 0:25:44.800 kidney stones lead to kidney infection, gallstones lead to infection 0:25:44.880 --> 0:25:49.440 of the gallt water milk duct blockage leads to mastitis 0:25:49.480 --> 0:25:52.200 like that is a very common phenomenon, and that is 0:25:52.240 --> 0:25:55.480 what's happening here where you have blockage of your lymph 0:25:55.600 --> 0:25:59.840 system from this inflammation leading to fluid getting backed up 0:26:00.240 --> 0:26:03.760 in a limb, et cetera. And then that's anitis for 0:26:03.960 --> 0:26:08.560 bacterial infection, and that bacterial infection is going to cause 0:26:08.720 --> 0:26:14.360 a lot of inflammation, further damage and exacerbation of all 0:26:14.359 --> 0:26:18.520 the damage that's already been caused. And so secondary infections 0:26:18.520 --> 0:26:21.879 are a huge contributor to the overall disability that we 0:26:21.920 --> 0:26:23.520 see with lymphatic philriosis. 0:26:25.040 --> 0:26:29.040 Question about the swelling and sort of the timeline of symptoms, 0:26:29.080 --> 0:26:30.440 So I know that you said that you can see 0:26:30.480 --> 0:26:34.399 markers of infection even in people who are asymptomatic or 0:26:34.400 --> 0:26:39.720 without these more pronounced severe symptoms. But for those pronounced 0:26:39.760 --> 0:26:42.680 severe symptoms, is that usually like seven to eight years 0:26:42.720 --> 0:26:45.239 after infection, because that's sort of the end of the 0:26:45.280 --> 0:26:47.120 adult worm's life. 0:26:47.520 --> 0:26:50.600 It's a good question. I don't have a number like that, Okay. 0:26:50.960 --> 0:26:55.440 It used to be thought that children didn't get infected 0:26:55.440 --> 0:27:01.239 with lymphatic philriiasis. That is not true. But what we 0:27:01.359 --> 0:27:05.000 know now is that it's this is a chronic disease. 0:27:05.040 --> 0:27:08.280 So even though any individual worm might only be living 0:27:08.440 --> 0:27:11.880 for seven years, only seven is a long time. It's 0:27:11.920 --> 0:27:18.520