Ep 129 Lymphatic Filariasis: Hiding in plain sight

a desperate search for treatment. The journey for relief brought none and depleted her family's finances. One man used a razor blade. He made cuts in my leg, then used the suction device. He told me he had removed something. But if he took something out, why was the leg getting bigger and bigger. As Perhabs deformity grew, her circle of friends shriveled.

some infect birds or reptiles. Apparently they do not infect fish that we know of that we know of, good one erin and generally they have a pretty complex life cycle with an arthropod intermediate host, so at minimum we're talking about a two host life cycle, pretty classic for parasites. And the worms that we'll talk about today are all in the family Onco Circudae, which we've already talked about one other time in our River Blindness episode. Anco circavolvulus.

But today we're talking about three others. We're talking about Wuchereria bancrofty, Brugia or Brugia malai, and Brugia timori.

start with the L three larvae. So the third stage larvae are what mosquitoes will spit under the skin as they bite us in order to infect a human. Is spit the technical term for this Yeah, that's the official scientific term for a mosquito bite. They will inject from their salivary glands the l three larvae during a bite.

of a few different species. In the Americas, it tends to be qlex Quinca fasciatis, but eighties mosquitoes and Mansonia mosquitoes can also transmit the infection, especially in the Pacific in Asia and the Pacific, and these are predominantly Brugia species. These are also entire genera of mosquito. It's not just like one or two species that we're talking about here.

they can persist for their lifetime. So I imagine, though I don't know the details of how they do this in all of these various mosquito species as well, it is impressive that a single parasite can do so in so many different species of mosquito.

I don't know. In the case of the parasites that coslymphatic philoriasis, I can tell you that when it comes to the development within a mosquito, these worms have to molt twice within the mosquito host, and it's a process that takes between ten and twelve days or maybe even up to two weeks per some papers, before they are

then able to be transmitted to another host. So there is certainly time in there to exert kind of a selective pressure on that mosquito, and a mosquito has to survive for at least those ten to twelve days in order to be able to transmit the infection.

a lot more detail about our lymphatic system. Don't worry, but these microfilaria predominantly travel to our blood vessels, and during the daytime preferentially hang out in our larger blood vessels, and then at night, when mosquitoes are most active, they travel to surface blood vessels so that mosquitoes can more efficiently pick them up in their blood meals and then go on to transmit them eventually.

is most commonly transmitting it in that region. So, for example, in the Pacific Islands, where they're transmitted by mosquitoes that are more diurnal, you see the microfilaria out in the surface blood vessels more during the day than at night. Like they're just so well adapted. It's incredible.

and this damage is progressive. And so the predominant symptom of lymphatic philariasis is lymphidema, swelling in a limb or in a body part due to disruption of the lymph system. And this swelling, this lymphidema lends itself to secondary infections. Really really easy to get a secondary infection when you have so much stasis of fluid.

into the extracellular space. Any cells that kind of burst open and release all of their lovely liquidy juices, that's going to become fluid in the extracellular space. So it's fluid and large molecules like proteins, et cetera, hanging out in all of the space between our cells. This fluid eventually is absorbed into the lymphatic system and carried through these tubes, through these lymphatic vessels into our lymph nodes.

It kind of drains into our lymph nodes. Our lymph nodes are these areas where a whole horde of our immune cells, especially our white blood cells, hangout. Because the fluid that's traveling through our lymph it has antigens in it, it has pathogens in it, it has just a bunch

of junk. And so what our lymph nodes are doing are essentially cleaning it all up, filtering out all of the junk in this fluid, and then eventually running that fluid from our lymph nodes through our spleen which is like not really a giant lymph node, but kind of like a giant lymph node in a way, and then sending that fluid eventually back into our vascular system. So putting that fluid, once it's all cleaned up, back into

our blood vessels. Does that make sense what our lymph system is and does?

The adult worms live in these little nests. They make these little nests and because they need to exist in a space that is like our lymph node's job is to clean out pathogens, right, That's our immune system's literal only job is to prevent things like worms from living inside of us. So these worms are actively secreting compounds to modulate our immune system's response to them existing inside of us.

many years might have no clinical signs or symptoms. However, that doesn't mean that there's not some degree of inflammation happening within these lymphatics because of this infection, because of these worms, because they are producing these microfilaria that are bursting out of our lymphatics, running rampant and getting into

our blood vessels. And so what we see is that even in people who have subclinical disease, that is, they don't have any symptoms of lymphatic philariasis, if you look inside of their lymphatics, they do still have some degree of inflammation in the lymph system, and over time, eventually

people are at increased risk for overt disease. So the question that you asked is like, what triggers this, right, And while we don't fully know as usual, it's thought that it's related to the frequency and intensity of our eventual immune response to these worms, specifically the response to these worms as they die.

you have an increase in inflammation. That increase in inflammation causes lymphangitis, which just means like swelling inflammation in your lymph system, lymphatinitis, which is inflammation specifically in like the lymph nodes themselves, okay, and then that is going to cause activation of our immune response. And we've talked a lot on this podcast about that like inflammatory cascade, where once you have inflammation, you're going to have more swelling.

You're going to have this positive feedback loop that continues to upregulate these inflammatory pathways, which leads to more swelling and more swelling and more inflammation and importantly, more pain. This is a very painful process, and the frequency and severity of these attacks can then lead to chronic changes over time. Another factor that's involved in the development of this like symptomatic disease is a particular bacterial endosymbiant and longtime friend of the pod, h Wilbakia.

development of swelling of this lymphidema, this fluid stasis leads to secondary bacterial infections, and that process where you have fluid stasis, things not draining, and then secondary infections is literally how so many infections in our bodies happen, Like kidney stones lead to kidney infection, gallstones lead to infection of the gallt water milk duct blockage leads to mastitis like that is a very common phenomenon, and that is what's happening here where you have blockage of your lymph

system from this inflammation leading to fluid getting backed up in a limb, et cetera. And then that's anitis for bacterial infection, and that bacterial infection is going to cause a lot of inflammation, further damage and exacerbation of all the damage that's already been caused. And so secondary infections are a huge contributor to the overall disability that we see with lymphatic philriosis.

for seven years, only seven is a long time. It's the accumulation over time, right, of multiple infections, because generally people are not infected with a single or even a couple of adult worms, and so it's it's a process that takes a long time. But I don't have like an exact number on it, but you can think of it as very much a chronic disease if it is untreated.

of fever, pain, swelling. These are the times at which this lymphidema and this lymph system dysfunction is being exacerbated. And so each one of these attacks eventually like it just causes further damage to the lymph system that over time will lead to a finding called elephantiasis, which is something a lot of people may have heard of. And this is what happens when the lymph system has become so damaged that the body part that is being affected

is significantly enlarged. It's very swollen, and the skin over time becomes very thick, very dry, and discolored, so it either like darkens or can become kind of like a grayish tone. And then you can see these very large protuberances on the skin that are caused by dilated loops of these lymph vessels, essentially like redundancy trying to be able to drain all of this fluid but not being

able to. And then because there's so much swelling, this leads to these redundant skin folds that kind of fold over on themselves and create yet another environment that is just ripe for secondary skin infections. Right now, the two most commonplaces that we see this type of damage, this lymphedema is in the legs, the lower limbs, and in

the testes in people with testes. Hydroceeal, which is fluid accumulating in the scrotal sac is actually the most common complication, especially in people with testes, and again it leads to all of these same issues. It's just this lymph dysfunction that ends up accumulating fluid in the scrotum rather than a limb, but in addition to leading to eventual elephantiasis in the scrotum, this can also lead to other urologic complications like infections in the inguinal lymph nodes. It can

potentially cause issues even leading up towards the bladder. It can be pretty severe. And while predominantly this is a disease that's affecting the limbs and causing this swelling and lymph stasis and disease in the limbs, it's not limited to the limbs. Our lymph system is everywhere and it's draining all of the fluid in our body, and so lymphatic filiasis can also affect the kidneys. Filarial antigens that are released and traveling are eventually filtered by the kidneys,

and these can cause kidney damage. You can also have fistullas that form between the lymph system and the kidney, which essentially means like the lymph system starts draining directly into the drain system of the kidney, which means that you lose essential protein and fat because your kidneys aren't even filtering that lymph anymore. It's just being drained directly

into your bladder. Right and if the microfilaria as they're traveling through our blood vessels, right, the babies are traveling through our blood vessels rather than our lymph system, they can get trapped in our lungs and then release antigens that can cause inflammation in our lungs and can result in a cough and wheezing, especially at night when the microfilaria are more active.

function with. Yeah, so that's the main biology of lymphatic philleriosis.

have treatment. There are a few different drugs that are effective at eliminating this parasite from the body, and so the main stay of treatment, and I'll talk in a lot more detail in the epidemiology section about this idea, but the main stay of treatment across the globe is something called mass drug administration, and this means not even checking anyone for infection, but giving whole populations anywhere that is at risk drugs once or twice a year, depending

on the drug, to target and kill these parasite And what this does is it reduces the density of microfilaria in the blood, which then reduces the transmission to mosquitoes, which then reduces the spread to the population. The problem is that there's a few problems. One is that you need really high coverage, like sixty five to eighty percent

coverage of a population to effectively interrupt transmission. And because these aren't necessarily killing the adult worms and these worms are living in us for so long, you have to then keep this up for five to six years in

a row at least. Because filarial disease also often co occurs with other parasitic diseases, you also have to be very cautious about which drugs you use in which regions so as not to exacerbate for example, uncosyirchiasis or loiasis, which is another worm that infects the eyes.

severe lymphidema or elephantiasis. For those cases, it's all about prevention and treatment of secondary bacterial infections, right, so trying to prevent as best we can further exacerbation.

really a lot of ways to fix that. Whereas with a hydro seal, you can kind of close off the area that's allowing fluid into the scrotum and then potentially drain that scrotum and then prevent further fluid damage because it's not like directly the lymphatic system that's draining into the scrotum. It's like right, right, But for like the legs, which is you know, the most commonplace, it's not not really surgically correctable as far as I can tell. Okay,

So that's lymphatic fileriasis. I mean it's a really awful it's really horrible.

that often accompanies these parasites. That's what puts the neglected

in neglected tropical disease. So what I want to do today is to take us through that vast history of lymphatic philoriasis up through the period when medicine began to figure things out, and then rather than asking why we haven't completely eradicated or at least eliminated this disease today, because the answer to that is a multifaceted but also mostly comes down to there's no profit in curing this disease or preventing this disease, which is disappointing and depressing

and not surprising. But instead of doing that, I want to do a mini exploration of a potential target for treatment and what exactly is so cool about this target. In other words, what the heck is this old friend of the pod Wolbachia and why is it so important to filarial parasites? And how can we use that to our advantage? Yeah, all right, let's get started.

to answer. I read one paper that estimated that the most recent common ancestor of Ruscheria bancrofty and Brugia malai, which are the two species responsible for most lymphatic philoriosis and humans, emerged around four to six million years ago, which the authors pointed out was around the time that the common ancestor of humans and chimpanzees began to diverge. But I'm also not sure how well that matches with the hypothesized geographic origin of these parasites. But you know,

it's still question mark here, Okay. But the third, more localized species, Brugia timori, is also thought to be ancient parasitizing non human primates until humans ventured into their realm,

and it still parasitizes non human primates. The two genera Wucheria and Brugia are thought to have split from each other more recently, around six hundred and seventy five thousand years ago, but the larger group that includes these filarial parasites has ancient roots, probably diversifying around the time that mammals did and getting well acquainted with their numerous mosquito vectors. I feel like I just used a whole bunch of

words to say these parasites are old. But you know, I like to put a little precision in there, just be precise about what we don't know and how much we do know about it, which is not very much.

has its origins in cases of lymphatic philariasis. Others tend to dismiss that idea, and they're like, what evidence do you have. There's a lot of different reasons that this could have originated, Okay. Another alleged ancient representation of this infection is from one of the earliest sculptures, the Queen of Punt stella aka like stone slab, which depicts a

woman ruler visiting Egypt from the land of Punt. This stella was found in the funerary temple of the ancient Egyptian queen Hatshepsut from around fifteen hundred BCE, and since its rediscovery many researchers, particularly in like the mid to late twentieth century, they've had many things to say about the stella and the queen represented. So the Queen of Punt, whose name was Ati, is depicted with a body arms legs hips that's larger relative to those of the other

people on the stella. For decades, researchers decided that she must have a physical ailment in order to be portrayed in this way, and they would pathologize her appearance to a kind of ridiculous extent, like it wasn't conceivable to these authors that she just had thick thighs and wide hips. She must have had lymphatic p hilariasis, all based on one image, no skeletal remains, no writings, just this image.

And I think it's interesting because I came across the Queen of Punt described as like definitely a representation of lymphatic hiliasis, and then I found other papers where it was like, yeah, this is kind of controversial. And then I found another paper that was like, hey, can we stop pathologizing women in ancient representations when we have no reason to believe that it was representing a disease, Like was it part of a medical text or was it just a stone slab representing a visit from a queen

from a different land. But I think that this Queen of Punt stella and the discussion around it serves as a good reminder to just keep in mind how limited we are in making retrospective diagnoses of any kind, and to ask whether we're pathologizing something because of our own

biases or lack of context. Speaking of which, there's also the quote unquote curse of Saint Thomas, which was a belief held by Christian inhabitants of some regions of India that the swollen leg characteristic of lymphatic philariasis happened to those who martyred him. But anyway, aside from these more questionable ancient references to lymphatic philariasis, we have plenty of

unquestionable ones. Medical writings from ancient Persia, China, India, Greece and elsewhere clearly described the condition, although whether it was filarial or non filarial elephantiasis is harder to discern in these ancient texts, but in general it was seen as a shameful condition, often a punishment, although in at least the ancient Indian text The Shrew to Samhita, it was observed that high prevalence of the disease happened in areas

with lots of stagnant water. Kind of interesting observation considering what we know about mosquitoes now. So far in the episode, we've primarily been using the name lymphatic philariasis, but that's far from the only name that has been used historically to describe this infection, which, like I found challenging when trying to find papers about its history. Oh, I bet, because I would just have to search like lymphatic hilariasis and then and then like all of the variations that

it has recalled throughout the decades and centuries. So the other common one that you mentioned Aaron is elephantiasis, and so we use that now to describe like the particular symptom or manifestation, and so historically that was used as just sort of a coverall force swollen limbs. And it's not entirely clear when and where elephants began to be associated with the disease, because that is where it comes from, but it may have been in that Indian text I mentioned,

the Sushruda Samhita from around seventy CE. The author Sushruda uses the term slipota slee for elephant and PoTA for leg to describe the condition, and about a thousand years later, ancient Persian physicians were also using terms like doll, fheel or da o phil elephantine disease in reference to lymphatic philiasis. As to the why of this, like why elephants, some people have suggested it's to describe the changing texture or the changing color of skin inaffected areas, or the fact

that certain limbs would grow to a certain size. And I should note that elephantiasis was not used exclusively to describe lymphatic philariasis, but also other swelling or thickening of the skin caused by other conditions, such as leprosy, which was written about in ancient Greece. The first use of the word elephantiasis in English was I believe sometime in the mid fifteen hundreds, but even into the twentieth century, elephantiasis was and still is often used split into filarial

and non filarial elephantiases. Aside from elephantiasis, there was also a whole host of other local names for the condition Barbados, leg yamleg, Java, leg, malabar, leg, Saint Thomas leg, Buchnimia tropica,

sarcoma ucosum, and so on. And listeners of the podcast can probably guess what I'm about to say next, which is that the wide variety of names for the disease I think serves it as an indication of just how prevalent and widespread it was in the ancient world, and with global travel and trade ramping up in the sixteenth century and beyond, these filarial parasites were about to travel to strain new worlds, where they would find ample hosts

and suitable mosquito vectors to continue their life cycle mostly unchecked. The Transatlantic slave trade beginning in the sixteenth century led to Wischeraia bancrofty becoming endemic in some Caribbean islands as well as on the North and South American mainland. Lymphatic philariasis was actually endemic in Charleston, South Carolina, until the early twentieth century. As its distribution grew, so did the

medical community's interest in this infection. Over the preceding centuries, medical writers had, of course paid lots of attention to lymphatic philariasis, but they were mostly at a loss to do anything more than just describe it and try out some mostly unsuccessful treatments. For real medical progress on understanding what exactly was going on with this disease under the surface, A key piece of technology had to be invented and refined,

the microscope. A microscope. This tool is what French physician Jean Nicolaus de Marque would use in eighteen sixty three to inspect the milky fluid that he extracted from the swollen scrotle sac of an eighteen year old with elephantiasis I know awful. In the first major breakthrough on the infection in centuries. De Marque reported, quote attention was drawn above all to a little elongated and cylindrical creature that had extremely rapid movements of coiling and uncoiling end quote.

He wasn't sure what exactly he was looking at besides worms, nor could he explain why they were absent once the scrotal fluid had cooled down. The answers to those questions would have to wait for other physicians. Four years after Marque's report, Otto Edward Heinrich Wucherer Woockerer was in Brazil inspecting a urinary blood clot from someone experiencing bloody urine

and found similar worms. Woucherier was curious whether these worms were the same as those that Theodore Bill Hars had found fifteen years earlier to be the cause of Hematuria the aka the causative agent of schistasiasis BLARSA. One look under the microscope told him that he had some very different worms on his hands, but he wasn't sure exactly

what they were. He published his finding quote as an incentive for some of my colleagues, better qualified and more fortunate than I, to attempt to shed light on a disease, the ideology of which is still enigmatic today. End quote.

Filaria hominous sanguiness, which I found interesting. I know that names change, they don't stick around, but like, literally none of those names remained for very long to describe that parasite. At this point in the eighteen seventies, what we've got are some enticing pieces of information about a parasitic worm and the infection that it causes, but no comprehensive picture of how this parasite caused disease and how it was spread. Enter Patrick Manson. I feel like I must have mentioned

Patrick Manson. I'm sure that I have, and at least a couple of other episodes on parasitesianmiasis, yeah, dracunculiasis more. I don't know, but he's a pretty famous dude in the history of parasitology and medical entomology especially, and he owes a big part of that fame to lymphatic hlariasis. In the late eighteen sixties and into the eighteen seventies, Manson worked as a medical officer in the Chinese Imperial Maritime Custom Service, and as a result, he treated many

people with the infection. Seeing the full range of manifestations from what he called quote unquote scrotal tumor to classic elephantiasis and tropical chyleria like lymph in your urine, he realized that these conditions, which had been treated as distinct diseases for the most part, were actually all caused by the filaria worm that had been described by Lewis. Manson then went even further, suggesting that mosquitoes played a necessary

role in the transmission of these filaria. His first hypothesis was wrong, though, which is that humans got infected when they drank water contaminated by the filaria which had escaped from their dead mosquito hosts. He later revised this with some colleagues and got it right. He also suggested that the diurnal activity of the worms in the bloodstream was directly tied to the periods when mosquitoes were most active.

larger blood vessels like of the lungs and other places. Really, the only thing that he didn't do when it came to understanding the life cycle of lymphatic philariasis was demonstrate the presence of adult worms in patients with the infection. That honor would go to Joseph Bancroft, earning him the

Bancrofty in Wucheria Bancrofty. Side note, Woucheria wasn't originally the genus name, but Ucheria's colleague wrote in after the name was announced, saying, my friend also deserves credit for discovering this parasite.

manifestations associated with different species. Effective anti parasitic treatments were only developed really in the nineteen seventies, and they leave something to be desired considering the sometimes serious side effects associated with their use, as well as the fact that while many of them are great at killing the tiny larval worms of Microfilaria, they aren't super effective for the

adult parasites. This is what you mentioned, Aaron, So treatment has to continue for many years, like you said, five to six before there's a chance of stopping the transmission cycle. And there is some suggestion that resistance to these drugs might be on the rise, which is terrible, terrifying. Given all of this, we better start looking for alternatives, right right. That's where Wolbachia comes in. What the heck is wolbacchia.

It may sound familiar to you listeners out there because we've mentioned it here and there on the podcast before. A quick search of our transcripts shows that we've mentioned Wolbachia in our Dengae, chicken gunya, Rocky Mountain spotted fever, and of course our uncle ssarchiasis episodes. Walbacchia is a genus of intracellular bacteria, so they have to live inside cells that infects arthropods like mosquitoes and filarial nematode parasites

like Wicheraia bancrafty and Brugia malai. I feel like I haven't said those species names the same way twice throughout this entire episode so far. Anyway, Waalbacchia are extremely widespread, with an estimated sixty five percent of all insect species infected with Wolbacchia pipientis, and nearly half of filarial species in Oncocircudae are infected, including nearly all of those that infect humans and those that cause heartworm in dogs and cats, which we should do an episode on.

and filarial hosts. I feel like we've talked about this a little bit a little bit, and I'm just going to talk about it, probably repeat a little bit again, no great detail. In arthropods, they often act as reproductive parasites, affecting things like sex determination, sexual differentiation, sperm egg incompatibility, and even the cell cycle, while in filarial parasites, Waalbaccia are more in a teammate mutualistic role necessary for reproduction,

and that's generally how I found they're talked about. So for arthropod hosts, it's like Walbaccia can be detrimental to or at least like change things in a ways that's not necessarily beneficial to the arthropod host, whereas in filarial parasites they're necessary and it's like a mutualistic relationship. How weird, isn't that bizarre? Yeah? Yeah. Without Wolbacchia, many species of filarial parasites can't reproduce, and without their filarial hosts, those

Wolbacchia also can't replicate. And it's this key feature of the filarial infecting wolbacchia. That has gotten researchers so excited over the past couple of decades because if there was some way to kill the Wolbachia inside the adult parasites, say through the use of antibiotics, it may not kill the parasites themselves, but it will prevent them from reproducing.

That course is four to six weeks long, which, as you can imagine, is super logistically difficult, and taking doxy for that long is not recommended for children under the age of nine and people who are pregnant or breastfeeding.

Those are some pretty major hurdles. Fortunately, there has been some promising research done on alternative antibiotics that have shorter treatment regimens or more specifically, target wallbacchia and leave the other parts of the human microbiome alone, right, Like, you don't want to just continually wipe out your gut microbiome

for four to six weeks. Yeah, and then there's phase therapy, so possibly using bacteria phases, so viruses that infect bacteria to kill the Wolbacchia, and anyone who's interested in learning more about phage therapy should listen to our Antibiotics Part two episode for more of that story. In general. Yeah, but to me, the moral of the Wolbachia and lymphatic filariasis story is not a very surprising one at all.

It's just that the more that we invest in learning about Wolbachia, in identifying species differences among these filarial parasites, in disentangling the relationship between the mosquito vectors and these parasites, in developing treatment programs that take into consideration logistical ease and long term efficacy, and in understanding the tremendous social

and economic impacts resulting from infection. The more we do all of these things, the more we can reduce the burden that these ancient parasites continue to have on the tens of millions of people around the globe living with this infection. So, Aarin, tell me, where are we with lymphatic philiasis today?

so let's get into it. So, first of all, an important piece of context when it comes to lymphatic philriasis is that in nineteen ninety seven, the World Health Organization classified this disease as erradicable or potentially irradicable, which I think we've talked in previous episodes about like what makes a disease a good candidate or a good target for eradication, But it's a lot to do with how it's transmitted,

whether it can infect non human animals, et cetera. So in any case, the World Health Organization said, yeah, this is one we could do this, and in two thousand they created the Global Program to Eliminate Lymphatic Fileriasis and they pass a resolution with a goal to eliminate the parasitic infection of lymphatic philriosis by the year twenty twenty. This isn't that story, it's not eliminated spoilers, But let's

talk about where we were and where we are. So where did things stand in the year two thousand and where do things stand now in the year twenty twenty three, three years after this elimination target. In two thousand. Before this program, it was estimated, depending on which paper you read, that's somewhere between one hundred and twenty five to two

hundred million people were living with lymphatic philariasis. Most papers were around the one hundred and twenty million people estimate, but at least one was two hundred thousand.

disease have we potentially prevented? Yeah, because when you think about it, especially in the case of lymphatic philoriasis, the mainstay of these programs was and remains mass drug administration of these anti parasitic drugs that sure can prevent the progression of disease, but primarily are designed to interrupt transmission. And what interrupting transmission does is prevent people from getting infected or from getting more infected than they already are.

These campaigns were not and are not curing disease for those who already have damage done. It's not fixing the damage causing lymphianema, causing eventual elephantiasis, right, And so in public health, one of the things that can be really difficult is quantifying that impact. Because if you're doing a good job in public health, and we've talked about this before, you're preventing things from happening. And if you're doing that, you're not like making money, which is what agencies care about.

You're saving money and saving lives and preventing disability. But it's really difficult to measure that because you're measuring things that don't happen rather than things that do happen.

administration programs have had on the global burden of lymphatic philoriasis, specifically at three different cohorts of people. First is people who are protected from ever getting infected in the first place. Secondly is the cohort of people who had disease but are being protected from progression to symptomatic disease, which is like secondary prevention. And then thirdly is that those you

are preventing from having even worse morbidity from this disease. So, based on this paper, the estimates are that between twenty and twenty twenty, this program has benefited a total of fifty eight and a half million individuals, six million of whom that's forty four percent are primary prevention. That's twenty six million people who never got infected as a result of this program.

from getting worse and worse and worse. So what that overall looks like is the prevention of an estimated forty four million cases of symptomatic lymphatic phileiasis, symptomatic hydroceal or lymphidema. And if you project that over the lifetime, it's estimated that these programs have averted two hundred and forty four million dollar disability adjusted life years. So like, you're not seeing that progression of disease. Does that make sense? Yeah?

of disease, primary and secondary prevention, which is really incredible. Now, what's important is that these are models, and like all models, they're only as good as the data that is input into them, and inevitably the data that existed prior to the start of these campaigns was limited in terms of what the true prevalence was prior to any of these

controls and the baseline disease burden. And of course we are still talking about tens of millions of people who already have clinical disease, and these campaigns are not ever going to be enough to treat their conditions. So there is a huge need for accessible and adequate treatment and management even after the interruption of transmission for this chronic disease. Because despite how much progress we've made, there are also still, like you mentioned, Aaron, nearly a billion people who live

in areas that are still at risk. So where do we go from here? Yeah, like you mentioned, aaron. In addition to the mass drug administration campaigns, there is a promise of potentially targeting this bacterial and asimbiant Wolbachia. And I find it hilarious that I talked so much about this in the onco psarchiasis episode, because I don't remember that, and because nothing that I saw talked specifically about using

antibiotics per se to target it. But there have been an effort to produce vaccines that specifically target Wolbakia rather than vaccines that target the filarial worm itself. However, there's also a theoretical promise for the development of vaccines to target Worschharia bancrofty specifically, although most of the vaccines under development use Brugia as their model because it's easier to grow in other animal species, so it's easier to use in the lab.

vaccine that actually prevents infection. So far, the studies that have been done have at least suggested that any vaccine that is developed would have to be a multi antigen vaccine because anything that they've tried so far that targets just a single parasitic antigen definitely hasn't worked, which makes sense when you think about how complex and interrelated the relationship between this pherasite and our immune system is at baseline.

So all that is to say that there is a lot of work being done to try and develop novel therapies and novel vaccines to try and reduce the burden further of this disease, but it remains the second leading cause of disability worldwide, and a huge cause of stigmatization and ostracization in so many parts of the world, predominantly in parts of the world that are incredibly impoverished and have limited access to healthcare already. So that's lymphatic philriosis sources. Sources.

People can read so much more.

Nursing Clinics from twenty nineteen. And if you want to know more about that math modeling study which was an excellent read, that is from Parasites and Vectors twenty twenty two and it was titled a Refined and Updated Health Impact Assessment of the Global Program to Eliminate Lymphatic Philariasis. But we will post all of our sources from this episode and every one of our one hundred something or other episodes on our website, This podcast will Kill You dot com under the episode's tab.