This Podcast Will Kill You - Ep 39 Toxoplasmosis: Calling All Cats

Episode Date: December 10, 2019

You’ve seen the headlines: could this cat-associated parasite be controlling your every move? Is the love you have for cats pure or merely a manipulation? Join us as we discuss Toxoplasma gondii, the feline-associated parasite that infects a whopping one third of all humans. Yes, you read that right. From the behavior-altering effects on rodents to the ancestral origins of the domestic cat, we dive deep into all things toxoplasmosis, the disease that sounds like it comes straight out of a sci-fi novel. See omnystudio.com/listener for privacy information.

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Terms and Conditions Apply. Visit blueapron.com slash terms for more information. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy. Sounds great, but a lot of these quote-unquote fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies, just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies. 100% human grade, real ingredients, beef, sweet potatoes, green beans, delicious.

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With the all new Audi Q3, the answer is always yes. Yes to adventure. Yes to escape. Yes to right now. The all new Audi Q3 made for the yes life. I contracted toxoplasmosis in my first trimester. I will never know how. The doctor did not educate me or test me for it. I was not given the opportunity to prevent the devastation this disease would have on my baby. It had a lot of time to go unchecked and do a lot of damage. My daughter Dana was born six weeks premature with severe damage to her brain and her eyes. She is now 22 years old. She has very little cortex to her brain. She has cerebral palsy. She is blind. She has severe developmental delays. Dana requires our full care. She cannot sit unassisted, walk, talk, feed herself, dress herself, or toilet herself.

My husband and I still change her diapers day and night. The toll on her body has been tremendous. She has had 10 surgeries, two of which were so traumatic we almost lost her. She has a tube that drains excess fluid from her brain. She has a metal rod in her back to help straighten severe curvature of her spine so her organs and lungs can continue to function. She has a pump surgically inserted to give her constant doses of a medicine to help her relax her muscles from further contorting her body, which, by the way, is only minimally

successful. One hip was reconstructed, the other is currently dislocated. I hate what toxoplasmosis has done to my daughter. It has stolen the dreams I once had for her, and from me. Our whole family has experienced emotional and financial strain. Yet through this all, we have loved this young lady. She is remarkably determined to endure. She laughs. She enjoys being a part of an active family life. Dana has a younger sister, Rebecca, who is in college right now. She is one of the smartest, wittiest, kindest people I know. Life has been difficult for her, too. Watching Rebecca, I can't help but think of what Dana's life would have been like if her infection were caught early on.

What would her future have held? Oh, my God. Yeah. That was an account by Janet Morel, who testified before the Illinois State Senate in support of Senate Bill 3667, which was the proposed prenatal and neonatal congenital toxoplasmosis prevention and treatment act. Act, this bill would provide that healthcare professionals shall provide counseling for toxoplasmosis and testing for toxoplasma gondi when providing care to a pregnant woman during her pregnancy. So that was part of her testimony.

Wow. My God. Yeah. It's a really, it's really sad. It's very rough. That is really rough. Well, I'm Aaron Welsh. And I'm Aaron Oman Updike.

And this is, this podcast will kill you. This week we are covering toxoplasma gondiae. Yeah, we are. Which has been a pretty heavily requested episode, I think. Has it? Yeah, I think it has. Yeah. And it's going to be a heavy one.

It's going to be an interesting one. It's going to be all the things that you've come to expect from this podcast. Yeah. Speaking of things to expect. It's quarantini time. It is. Erin, what are we drinking this week? This week we're drinking what the cat dragged in.

What is in what the cat dragged in? Well, of course, it's not a dead mouse, but that would be appropriate as well. It's vodka, some sparkling wine, a little crem de violette, and lemon juice. Yeah, it's tasty. But the crucial thing is that you rim the glass with pop rocks. Of course, because they look just like kitty. There you go. We'll post the full recipe for this quarantini as well as our non-alcoholic placebo

rita on our website. This podcast will kill you.com and all of our social media channels. So follow us there for the full recipe. And I think I want to cover a couple pieces of business, which I just don't think that we have done. It all pertains to live shows or live-ish shows. They weren't live-ish. Like we were there.

Yeah. That's true. It wasn't like a full live show. We're not going on tour or anything like that. Sorry. We were lucky enough to go to both the University of Florida, thanks to Nick Kaiser, and also to the University of Michigan, thanks to Laura Haynes. Yeah. We met so many amazing people during both trips.

It was really, really fun. We had the most fun at both of those trips. It was super excellent. So thank you for inviting us and thanks to everyone who came and watched. It was so fun. Yeah. It was great. And also, I recently, Aaron Welsh, I was recently a guest on a live show of a podcast called The Road to Now. Yeah, yeah.

It was super fun. So this is a really great history podcast. And they came to Chicago recently and I got to be a guest along with Obama's White House photographer Pete Sousa. So. It's so great. Mind blowing. So cool. Surreal.

But anyway, you can hear that episode of the live show on the road. road to now. So just look them up wherever you get your podcast. And we're also going to post a link if we haven't already by the time this comes out on our social media. Yes. Any other business? We have a new merch including water bottles. Yes. They're gorgeous. They're very, very cool. And they're the nice, like, insulated kind, metal water bottles and fancy smelling soap. New smells of soap. New smells. So check that out. Just go to our website. This podcast will kill you. and click on merch to find that. Any other business?

Nope, let's just dive right in. Okay. Erin, tell me about the biology of toxoplasmosis. I just can't wait to do that. We'll take a little break. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients, so there's no

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repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works.

O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit O'Keef's Company.com slash this podcast and code this podcast at checkout. A timeless wardrobe starts with pieces that are built well from the beginning. From the fabrics to the fit, everything needs to last beyond one season. And that's how Quince approaches design.

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Refresh your wardrobe with Quince. Go to quince.com slash this podcast to get free shipping on your order and 365-day returns, now available in Canada, too. That's Q-U-I-N-C-E-com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. Toxoplasma gondia. Toxoplasmosis. I've been looking forward to doing this episode ever since I was a guest on the percast. Oh, yeah. Yep.

We talked a little bit about toxo on that episode. If you haven't heard it, it's really fun. But I didn't do any research on toxo before I went on the per cast. So I felt really silly because I didn't know the answers to a lot of questions. So I'm excited to finally, you know, have done some research on this. Like, actually know what I'm talking about a little bit. Still not an expert. Okay.

Polished amateur. Exactly. That's a good description for like my life, I think. Okay. So toxoplasma gondi is a protozoan parasite. So like malaria or giardia. Oh, you did a great job. Thank you.

Is that condescending enough? Just a little. So this is a single-celled organism that's not a bacteria or a virus. Okay. Yeah. And this, when I learned this fact, blew my mind so hard that even though this is technically epi, I'm going to say this up top. Toxo infects up to one third of the entire world's population.

Uh-huh. One-third of the globe of humans. Uh-huh. I know. I know. It is just mind-blowing. It's so wild. Oh, my gracious.

Okay. So, because this is a parasite, we have to talk about its life cycle because it's more complicated than some other organisms. Okay. So the main host of toxoplasma gondi is, of course, cats. Cats are the definitive host of toxoplasma gondi. And when they get infected with this parasite, they poop out thousands and thousands of something called oocysts. That's the life stage that the cats poop out. Okay?

Yeah. And after one to five days in the environment, the environment being cat poop, so cat box or your sandbox where your kids are playing or your backyard or pretty much anywhere in the environment, these oocysts sporulate. So then they kind of become infectious at that point. Once they sporulate, they can persist alive and infectious in the environment. for years. Really? Well, at least a year. Okay, for a year?

Yeah, for months and year, depending on the environment. So they can get into the soil, they can get into the water, they can get on your vegetables, etc. What's the ideal environment? The ideal environment would be kind of subtropical, so not too hot, not too cold, although they can survive freezing. You know, no big deal. Yeah.

But they do, like, we'll see in the episection, burdens tend to be highest in warmer climates because they do persist better in warmer climates. Okay. So they get all up in the environment and then they're picked up by small animals, birds, mice, rats, generally things that cats might like to feed on. Once they get into these small animals, they are now called tacky-zsche-es. zoites. So that's the life stage that infects small animals. Okay. I want to make some sort of joke about tacky, but I'm coming up blank. I tried. I tried too. There's, there's no good one. So inside of a mouse,

generally the way that a small animal gets infected is by coming into contact with their mouth. So they eat some soil, they drink some water, they eat a piece of lettuce, whatever it is that has these tachy zoites on them, and they get infected. Then these tachyzoites burst out of the intestine of these mice or these rats, and they infect tons of different cells. So this is a parasite that is actually, it has to be intracellular. So it invades cells inside of everything that it infects. And this life stage replicates asexually, so it just divides, and it does so really, really

rapidly and really profusely. So in the mouse, you've now got this parasite dividing and replicating and swarming through the tissues. Then they'll find their way into two specific tissues that they like to invade, muscle and brain. Why do they like those two types of tissues? Well, let's talk about it. I like how now you like, you know me so well that you know what I'm going to ask. Most of the time. Doesn't mean I always know the answers, though. But here we can talk about it. So they find their way into neural tissue and muscle tissue. Once they're there, I'm going to first say what they do once they're there. Then we'll talk about why these are the tissues they invade. Once they're there, they insist. So they actually transform into yet another life stage, the Bradyzoite. The Bradyzoite forms a cyst inside of the muscle tissue or the brain tissue. The cysts, is surrounded by the animal's tissue, muscle or brain, but then full of hundreds of these Bradyzoites, these continue to divide, but they do so much more slowly. Okay.

Okay. But then to complete the life cycle, these Bradyzoites have to find their way into a cat. Right. So the cat is going to eat the mouse or the rat or the bird. What part of the mouse or the mouse? the rat or the bird, do cats definitely eat muscle tissue? That makes sense. Okay.

So that's why they insist in the muscle tissue. Why might they insist in the brain? I think I know the answer to this. Oh, yeah. It turns out that toxoplasma gondii is a parasite that can exhibit behavior modification. So that means that it can actually change the behavior of the animals that it infects. which is... It's really cool.

It is very cool. It's kind of like blows the lid off of the whole parasite host dynamic in a way that is so sci-fi, but also I think it's just the tip of the iceberg. Okay, I'm jumping the gun. I'm too excited. It is so sci-fi, but it's something that's actually not that uncommon in parasites that are transmitted what we call trophically. So from one what we call trophic level to another. So if you think of like the pyramid of life with like carnivores on the top, carnivores are going to eat herbivores and herbivores

are going to eat lettuce or whatever, right? Primary produce, secondary produces, primary producers. Exactly. Right, right. Lettuce. And so in in parasites that are transmitted like through the food chain like that, it's actually not that uncommon for parasites to manipulate the behavior of that intermediate host, like the mouse, so that they're more likely to be eaten by the definitive host, i.e. the cat. In the case of mice and rats that get infected, what they do is not only do they seek out more rapidly novel environments and they're less fearful and more likely to be in open areas where normally mice and rats are kind of like they stay hidden because they don't want to be eaten for example. So infected mice and rats will seek out novel areas and explore more readily

and they've done studies that show that they're not only less afraid of cat smells like cat urine, they're actually attracted to smells like cat urine. Yeah. Isn't that it's really yeah it's it's almost unbelievable like when you think about that the parasite has evolved to be transmitted this way and this is how and so here's the reason why this happens or a reason why this happens is that only in cats can toxoplasma gondi complete its life cycle because once a cat eats those brady zoites that are in the brain or muscle tissue. Inside the cat, they actually undergo sexual replication. And only in cats do, does toxoplasma gondii actually sexually reproduce? And then it produces those oocytes that the cat poops out and then the cycle can start all over again. Right. The parasite has to find its way

back to the cat. Yes. Yeah. So there's a huge amount of incentive on the part of the parasite to make sure that they make it into the cat. Yeah, it's gorgeous. It's beautiful. It is. That being said, what about humans? Yeah. So that's the life cycle, like, in the wild or in whatever. That's how toxoplasmogondiae evolved to exist. So what are humans? Are we the cat or are we the mouse? The mouse? We're the mouse. So it turns out that we can get infected with almost any life stage of the parasite. So we can get infected directly from those sporulated oocysts that cats poop out. So that means if we get in contact with cat poop directly or with contaminated soil or contaminated water or maybe contaminated vegetables that haven't been washed or

cooked, then we can get infected with that first stage, those tachyzoites. Okay. Those are the stage that's going to invade tissues locally that's going to replicate really rapidly. But we can also get infected with those tissue cyst stages that would normally want to be eaten by a cat, the Bradyzoites, inside tissue cysts. Gotcha. So if you eat contaminated meat, for example, then you can get infected with that life stage. However, since we're not cats, the parasite can't complete its life cycle inside of humans. We're a dead end host, just like in Lyme disease. Just like in Lyme disease.

We're not contributing to the parasite life cycle and like the prevalence. Unless a cat ate us. Which does happen. Could happen. Yeah, could happen. And it definitely happened prehistoricly. For sure. Apparently cats were like a major, major predator of humans, or like of the ancestors of humans,

which makes total sense. Fascinating. Yeah. Yeah. Okay. So in humans then, the main way that this parasite causes disease is in two main ways. First, by invading cells and tissues. So it can cause direct damage in those tissues that it invades.

And by forming tissue cysts in really important places in our body where you shouldn't have cysts full of parasites. Cool. Cool. I mean, not cool. But yeah. Okay. Got it. All right.

So let's talk about the symptoms that we see in toxoplasma infection. The good news is that the vast majority of people who get infected, something like 80 to 90 percent of people, will be entirely asymptomatic. That's it. For some reason, I expected it to be higher asymptomatic. You said 80 to 90 are asymptomatic? Yeah. Yeah. Okay.

Yeah. But, okay, so even of those 10% of people who, you know, maybe do show symptoms, the vast majority of those people will have a very non-specific self-limited illness. So they'll feel a little sick, kind of cruddy. And the most classic sign of an initial toxoplasmosis infection is lymphadenopathy. So your lymph nodes get swollen. Okay. And that's pretty much it. Those lymph nodes usually aren't very tender and they can stay enlarged for like a month or so. The vast majority of the time. So that's even if you have symptoms, the vast majority of time, that'll be kind of your only symptoms. So not that big of a deal in that case.

However, in some cases, a primary infection can invade specific organs and then cause illness in those organs. So if those tachy zoites swim through and find, say, your heart, you're heart tissue. Your heart is a giant muscle. So it wouldn't be surprising for them to try and find and insist in your heart muscle. Then you could get something called myocarditis, which just means inflammation of your heart muscle. If those tachyzoites invade your lungs, you might get a pneumonitis. If they invade your liver, a hepatitis. All of these are theoretically possible. They have happened, but they don't happen very commonly. Is there anything?

So I know like immunocompromise is one big aspect of where this might happen more than others, but is there anything else that makes you more susceptible to organ invasion? That's a really good question. So the only other thing besides immunocompromise, which I'll talk in more detail about in just a second, is potentially strain differences. So there are a number of different like genotypes and strains of toxicoplasm, the gondi, and there is some difference in virulence between those strains. How big of a role that plays is not entirely clear. Okay. But so, yeah, for most people who are healthy, they will never

have any signs of infection. But in people who are immunocompromised, especially in people living with HIV, toxoplasma can be an extremely serious infection. The most of the most of the most of, the most common form of toxoplasma infection of toxoplasmosis in people living with HIV or people who are otherwise immunocompromised is encephalitis. So that's inflammation of the brain. So here's the thing about toxoplasma. If you get infected, even if you're asymptomatic, it doesn't necessarily mean that you don't have cysts inside of you right now. But most of the time, your immune system is going to be able to keep those cysts kind of in check. They're never going to do anything. They're never going to cause harm. But if you become immunocompromised, those cysts can reactivate, essentially. And then you can get

the encephalitis later on. Okay. That's bad. So you can, like, if you have an immunocompromise, you could get sick with toxoplasmosis from a primary infection. Like, this is the first time you got infected, or it could be that you've had cysts in your tissues and now they're reactivating because your immune system is low. It's really, really serious. It's considered an AIDS-defining illness, toxoplasma, encephalitis. Got it. In a person living with HIV.

And then, of course, the other way that you can get infected besides eating contaminated meat, which, by the way is the most common way that people do. get infected. But I do have to point out there was a study that looked at the rate or the prevalence of toxoplasmosis in people who were vegetarians and people who were not vegetarians and found equal rates. Fascinating. So yeah. So it's very, very clear that there are many different routes for exposure. Absolutely. Much, much beyond cats as well, much beyond owning a cat, I should say, as well. Owning a cat is generally not even alone. Owning a single cat is not even considered a risk factor. Right. And we'll talk more about the ecology of that and why that is. Yeah. But the other way

that you can become infected is congenital toxoplasmosis, which is what we heard about in the first-hand account. It is horrible. So toxoplasma can cross the placenta and then infect the fetus. It turns out that this is most common if a pregnant person gets infected for the first time while they're pregnant. And what's interesting is that the risk of infection of the fetus actually increases with gestational age. So the later in a pregnancy that a person gets infected, the more likely it is that the fetus will be infected. But the severity of that infection is opposite. So it decreases. So the earlier a fetus gets infected, the more severe the outcomes.

But the less likely they are to become infected. Exactly, right. So overall, without any treatment for a primary infection, so a pregnant person who gets infected while they're pregnant, the risk of congenital syphilis is between 20 to 50 percent, depending on when during their pregnancy they get infected, what strain they're infected with likely and how much they're exposed to probably as well. Severe infections can result in fetal loss, so it can result in stillbirth or miscarriage. But other characteristic findings are things called corioretinitis, which is inflammation of

the retina and the choroid, which is basically like your blood vessels in your brain, in your eye, sorry, not your brain, which can lead to blindness. hydrocephalus, which is the buildup of fluid in the brain, and intracranial calcification, which is calcium deposits essentially inside of your brain, and then seizures in a baby. So, yeah, it's really bad congenital toxoplasmosis. Is it routine anywhere to screen?

It's not routine in most places to screen unless there is risk for infection. So it's not, it's not universal. And is it something where you could determine whether it's an active infection or a, like something that you have been infected with, and the cyst are just there? Yes, you can. So in general, and I will say that pregnancy is a form of immunocompromise, so it is possible to have re-activation of cysts, but it's much less likely that that will result in congenital toxoplasmosis. Okay. So it's really that primary infection.

Like if you get infected for the first time while you're pregnant, that's when it's the highest risk for... So it's like the tachyzoites? Exactly. Right. Yeah. But also even if you like ate pork that was infected, so then you're getting infected with Bradyzoites, but it's just not from within your body reactivating. Gotcha.

But it's that primary infection, yeah. But yeah, we usually use zero prevalence, so looking for antibodies, but you can tell based on the type of antibody and the amounts of antibody, whether or not it's a primary infection or you were infected, say, 10 years ago or something like that. Okay. And the good news is that there is treatment. The treatment is mostly aimed at that tachyzoite stage, that rapidly dividing stage, so it doesn't affect the tissue cysts directly. So that's kind of the catch 22 is that we can treat it, but we can't really affect those tissue cysts. But if there's an act, like let's say for pregnant people, if there's an active infection, that's really the thing that needs to be targeted anyway, it appears?

Yeah. And so for pregnant people, there's two different ways that we can treat it, depending on if we think the fetus is already infected or if we're trying to prevent the fetus from getting infected. So one, you can treat just to prevent those tachyzoites from kind of crossing the placenta and infecting the fetus. Or if you think the fetus is already infected, you can give different drugs that actually help treat it within the fetus itself. And all of those are affecting the tachyzoite stage as well. Okay. So, yeah, I mean, that's basically the biology of toxoplasmosmosis.

Oh, okay. Yeah. It's a bad one. that it was bad, but, um... Yeah. Yeah. So, Erin, how did we get here? Where did this thing come from?

And why does everyone get infected? One third of all people. I'll tell you, after this quick break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream.

that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments.

It's been relied on for decades by people who wash their hands, constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefe's. Just visit O'Keef's company.com slash this podcast and code this podcast at checkout. This is Bethany Frankel from Just Be with Bethany Frankel.

Listen, I have a bone to pick with these dog food. brands calling themselves fresh, natural, healthy. Sounds great, but a lot of these quote-unquote fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies, just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies, 100% human grade, real ingredients, beef, sweet potatoes, green beans, delicious. These are foods that you would want to eat, not that the babies would ever share. Just food for Dogs is the number one bet recommended fresh dog food back by over a decade of research. No marketing fluff. My dogs lose their minds at dinner. They run to the bowl, tags wagging,

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Indeed.com slash podcast. Terms and conditions apply. Need to hire? This is a job for Indeed. D's sponsored jobs. So the actual written history of toxoplasma gondii is just over 100 years old. That's it? Yeah, like the written history of there's this disease that does this, there's this parasite

that does this. Wow. Yeah. So this is going to be a really short section. Just kidding. It's not. It's you. Yeah, it's me.

It'll never be a very short section. It just means I'm going to talk more about evolutionary history and other things that I'm just going to sprinkle throughout. Fabulous. Okay. But let's get to the written history part of it first. In 1908, the parasite was described for the first time. There were these two researchers working at the Pesture Institute in Tunis. They were studying Lechmeniasis, which is a disease caused by a different protozoan parasite. They're trying to figure out what the reservoir host was and learn more about the Lechmania transmission cycle, all of these things. And for their research, they were using an animal called a common gundi.

Oh, what's that? I had no idea. I looked it up and it's like kind of weirdly cute. It's definitely not like that cute. I mean, that's horrible. We'll post a picture? Yes, of course. And so this is, it's about the size of a guinea pig maybe,

and it's a type of rodent that's native to northern Africa. Oh, okay. It's super good at living in rocky deserts. Okay. And so they were looking at this, the tissues of, of a Gundi, Gundy, for parasites, Lechmania, and they found a protozoan that they thought was Lechmania. But they looked a little bit closer and realized, based on morphology, this is a completely different parasite.

Awesome. So they named it toxoplasma gondi. Toxo, for the Latin word for arc, plasma for former life, Gandhiyai was a misspelling of the host. Gundy? The common Gundy. No way. G-U-N-D-I is how you spell the animal. G-O-N-D-I is how you spell the specific epithet of toxoplasma-Gaudi.

That is so funny. Yeah. I love it when things get named for silly reasons like that. I mean, it's one letter, but it's just kind of like, I never thought about Gondi. I just thought probably it was going to be someone's name. Yeah. Wow. That is so interesting.

Anyway. Okay. So at the same time that these two researchers, who, by the way, their names were Charles Nicole and Louis Mansoe. At the same time that these researchers were finding and describing toxoplasma Gandhi in the common gundi on the opposite side of the world in Brazil, another researcher, same year, another researcher named Alfonso Splendor was doing the same exact thing. Like he found toxoplasma Gandhii, but he found it in a rabbit.

What? Instead. Same time. Same time. Yeah. Keep that fact in your head. Ooh. They're going to be drama? No, I mean, not really. I will say that by and large, Nicole and Manso are the two that get the credit for the discovery. And in large part because their finding was written in English.

And Alfonso Splendor was his was written in Portuguese and not translated into English until 2009. And so this goes into the whole English as a dominant. And as the only scientific language and blah, blah, blah, all the issues surrounding that. Wow. It's kind of interesting. He also didn't name the parasite. He just said, I found this parasite. Okay.

So that could have something to do with it, too. But another 30 years would pass before people realized that this parasite could be harmful to humans. Okay. It was in 1938. Wow. There was a three-day-old newborn. I was born at Baby's Hospital in New York City.

She started having seizures. And the doctors looked her all over, and all they could see that was out of the ordinary were these lesions in her eyes. Sadly, a month later, she died. And so during the autopsy, doctors saw the same lesions all over her brain. And they, you know, wrote a case study up about this. And this case study would end up being probably the first recognized case of congenital human toxoplasmosis. Because they found the parasites in her brain, and then they injected it into an anthonyl. animals and then they developed encephalitis and so yeah. Wow. And so at this point,

toxoplasma gandiae is a recognized pathogen, but there were still many mysteries surrounding the parasite, including the extent to which people were infected, like the prevalence, how they became infected, and many characteristics of the parasite itself, like its life cycle and its hosts. So researchers had detected the parasite in many different mammal species, but they were unsure of which animal was the definitive host. So which, yeah. And at first, they suspected it had something to do with eating undercooked meat, which, as you said, it definitely does. And so in the 1960s, these group of scientists designed an experiment in which they fed essentially raw lamb, like just barely cooked lamb chops, to people with tuberculosis living at a sanatorium to see if they could

transmit toxoplasmogandiae. I'm sorry. Yeah. Every episode this season is going to have some horrible experiment that we've done on humans. Yeah. Well, and the experiment was successful. Of course. They killed a bunch of people. They didn't kill people. Okay. But these people did become infected. But that didn't quite answer the question of what the definitive host was. It was just like, can you get it from uncooked meat? So a few years after this experiment, a parasitologist decided kind of on a whim to check out whether his cats had the parasite. Bingo, they did. And it didn't take long for other labs to confirm these findings.

And then this is like in the early 1970s. And the backlash was, there was like a strong backlash against cats. Apparently, according to one of the articles I read, there was like a lot of people, and I don't aware exactly or how many killed cats out of fear thinking these cats are killing my children, these cats are killing, you know, through this parasite. But I think for the most part, that was not the common response. I think it did happen, but I don't think it was the common response because cat ownership has only continued to increase since that study was released.

So after finding that felines are the definitive host for toxo, a lot more of the pieces began to fall into place. So the complex life cycle of the parasite was figured out, and people started to get an idea of how it causes these behavioral changes in rodents that influence the parasites' transmissions. So cool. It's so cool. And it's these early studies on the behavioral influence of rodents that really opened up this huge field of research about behavioral manipulation of parasites and what that might mean for humans and our microbes. So I'll get to that in a bit. it. But that's basically the written history of toxo. Wow. So short. It didn't cause any massive

pandemics or overtly change the course of history in some dramatic fashion. And it isn't even old enough to have any like bizarre cures associated with it. It just basically consist of a series of scientific developments and findings. But there is more to toxo than that. Yeah. Like where did it come from? Exactly. So remember how. the parasite was discovered simultaneously at two different points on opposite sides of the world. Yeah. So. There's a certain amount of coincidence that goes into that. But really, what it tells us is just how incredibly widespread this parasite already was. Yeah. Like that wasn't new at that time.

That wasn't new. So the question is, how did it get to be like that? And the answer is domestic cats. That truly is the answer. So, I mean, pure. Yeah, let's go back in time. Let's go back to around 11,000 years ago. So it's around then when we see the very first evidence of agricultural societies. So people actually settling, keeping livestock, growing grains and plants at home. And we see this happen in different places all around the world over the next several thousand years. So in the Fertile Crescent is where it began, then in China, then Mexico, then Western Africa, and so on. So, around like 11,000 years ago to 4,000 years ago is when like the biggest, you know, movement or

shifts started to happen. And I've talked on this podcast before about how the formation of agricultural societies and farming, how that would have impacted disease transmission and what types of diseases were transmitted and what they would look like. Right. So, you know, just a refresher, larger human settlements means more transmission between humans. So you get these crowd diseases like tuberculosis and influenza. And then you also get zoonotic diseases transmitted between humans and their livestock or humans and domestic animals. Yeah. And the human animal contact increases not just because of people choosing to own cattle or whatever other livestock, but also because of keeping large stores of grain and other food. Yeah. And then you get other little animals

finding you. Like mice and rats, etc. Exactly. For example, the house mouse. So there's archaeological evidence of the increase of the house mouse as human settlement increased, human agricultural settlement increase. So 12,000 years ago, the proportion of house mice bones found among small mammals near hunter-gatherer communities was about 5%. Okay. But within a thousand years, which is like a long time but also a very short time, that number jumped up to 80%.

So like of all the animals that they found near, like 80% of them were house mouse. House mouse. Way to go, Aaron. Isn't that wild? Yeah. That's a huge change in a thousand years. That's a massive. Yeah.

So it's probably a good thing, or at least no surprise, that cats were domesticated in the Fertile Crescent around the same time that agricultural societies began to form there 11,000-ish years ago. Because there were so many mice for them to eat. Yeah, it's probably not coincidental. Yeah, no. But anyway, so there was a little cat named the near-eastern wild cat,

who even like the wild populations today seem to be very bold and not very aggressive towards humans or fearful, which is kind of interesting and makes sense. So these types of cats came up to human dwellings and they made themselves at home and probably in a way that's familiar to a lot of cat owners today. Just like, hi, I'm here now. I'm here now. I will live here. And so this caused a major shift in the dominant transmission pattern of toxoplasma Gandhii.

The sylvatic cycle, which is the natural cycle in the forest basically or in the wild. Like wild cats. This is the one that still seems to be quite active in many places today. So this involves the wild phelids and wild rodents, while the domestic cycle is the one that we are more familiar with. And it's the one that has led to the huge prevalence of toxo around the world today. This is the one that involves our house cats and house mice. And scientists have looked at the genetic diversity of toxo around the world and have found that in urban areas where the domestic cycle dominates, there's less diversity because there's more mixing of the parasite populations.

And that's in contrast with the higher diversity seen in places where the Silvatic cycle is more common, such as the forests of Central and South America. But overall, the domestic cycle is the more common one, and the simple answer for that is house cats. So felines are the only animals that can serve as a definitive host, as you said, and wild felines have never really been at high enough population densities around the world to be able to result in the widespread and extremely high prevalence of toxo. In humans. In humans.

Yeah. In humans. Yeah. But also in places where wild cats do not occur, we still see a ton of toxo. Yeah. In other animals. In wildlife. Right.

Yeah. I'm not surprised about that. And that is largely due to house cats as well. Why were cats domesticated in the first place? To eat the mice? So that's probably part of it. it. So I read this book that's called The Lion in Your Living Room and it talks all about like, it's all about the history of the cat. It's very fun. And she is a huge lover of cats. And she's like,

you know, it just doesn't really make a lot of sense. Like dogs have tons of different roles. They have tons of jobs they can do. They're protective. They can work. They're useful. Cats, you know, they can kill rodents. But for the most part, cats, so can dogs. Yeah. And dogs are actually more effective at actually lowering populations of rodents. I didn't know that. Because there can be task oriented, whereas cats aren't as task oriented. And so they've shown, like, studies that cats don't often actually effectively reduce rodent populations unless food, other food, is extremely scarce.

Interesting. Because they'll go for the low-hanging fruit. They're lazy. Those lazy kitties. This is like, this is famously captured in a video. of cats scavenging for trash right next to rats. Because they're like, I don't want to waste my energy killing and eating a rat when I can just eat trash.

I mean, it makes sense. Who can blame them? And certainly now they do little to affect urban rodent populations. Right. So she did, though, so the author of this book, though, did, started a file apparently called Uses for Cats when she was researching this book. And I just want to list a few of these because they crack me up. Please.

So, first of all, they're. There was to encourage rain. People in Indonesia would parade cats around their fields. Parade cats. I love it. I wonder if parading cats is easier than hurting cats. I mean, it's probably equivalent. People use cat skin for musical instruments a lot.

Apparently, people in China used to use the cats dilating pupils to estimate the time of day. And they were also a critical part of. many types of European tortures. Ooh. So, I'm quoting directly from her book, medieval murderers were sometimes burned in a sack with 12 cats to maximize suffering. And during a punishment called cat hauling, a cat was dragged by its tail down the length of an offender's body.

Oh my God. Yeah. I feel so bad for the cats. I know. Okay. So then there's some more modern things. So cat hair has been used in DNA evidence. murder trials. Okay, okay.

Which is pretty cool. Yeah. So anyway, those were a few of the things on the uses for cats list. But, I mean, regardless of their questionable skills as rodent controllers or any of these other, you know, powers, humans kept them around. And that's maybe putting it mildly. There's archaeological evidence of the love that humans have for cats. There's a 9,500-year-old grave for a kitten on the island of Cyprus. Oh, baby.

There's, of course, ancient Egyptian artwork showing house cats, worship of cats. Didn't, weren't cats to ward off evil spirits and stuff? They're like protectors of the living. And then on the flip side of that, things weren't always so good between cats and humans. So I talked a little bit about it during the plague, but also cats in general in a lot of, during sometimes in a lot of places were thought to be. demons or agents of Satan. And some historians think that this might be due to the fact that allergies to cats are fairly high.

So like, if a cat jumps on you and goes around your face and stuff and then you all of a sudden your throat itches and you can't breathe, I mean, I would probably think, yes, this cat is like an agent of Satan. Anyway, wherever humans went, they brought cats with them, maybe as mouse or rat killers or maybe just as a good luck charm. And cats, of course, were especially valued on ships. And sometimes sailors would refuse to get on a ship if it was missing its resident cat. But when humans and cats traveled the globe together,

there was this other hitchhiker that tagged along, toxoplasma gondi. And the proof of how far cats have traveled is in the global distribution of toxo. Toxoplasma gondi is now found all over the globe, even above the Arctic Circle. Whoa. Yeah. And in there, it's found its way into beluga whales and other Arctic dwellers. And it's like quite a problem.

Yeah. And it's not just that where you find cats, you can find Toxo. Thanks to water, Toxo can travel incredibly far. And over the past 100 years or even 50 years, cats have grown incredibly in popularity. People have moved into apartments in citizens. Cat litter was invented, and globally now there are around 600 million domestic cats. That's not as many as I expected. Well, there are around anywhere from 600 million to 1 billion cats worldwide.

Okay, okay. And these aren't just pets. These are also feral cats. Right, right, right, right. And every day in the U.S., more cats are born than there are lions in the wild. Whoa. Yeah. That is a shocking statistic.

Yeah. And these cats aren't always pets. No. In Australia, for every one pet cat that has a home, there are six feral ones. That's bad. It's really, really, really, really bad. Yeah. And in the U.S., only about 60% of the American pet cat population are kept indoors.

Ooh, that's bad. Yes. That's really bad. We touched on this in the Kittred episode, but I assume we're going to talk a bit more about how important it is to keep cats indoors. Yeah. So it's not, I mean, it's not just that cats have single-handedly wiped out entire species, many different species, but even researchers have shown that even just their presence

alone causes many problems such as increased stress, making it difficult for some prey species to breed or parent properly. And they also spread disease, feline leukemia, toxoplasmosis. And for the most part, these problems can be greatly diminished or completely fixed by keeping cats indoors. Right. Cats have a huge cascading effect on the ecosystem. And then when you throw in toxo, it's a pretty big conservation and public health problem, outdoor cats. Yeah. And this is not easy to talk about.

No. At all. Because people love their cats and they love cats in general and they can feel defensive about this. And by and large, if you have a cat and keep it indoors, you're not part of the problem. Your cat's not part of the problem. Yeah. Strays and feral cats are much more problematic and finding a solution that works has not been

easy. Yeah. And in this book, the line in the living room, she goes into this in a lot more detail. But there's this, you know, a lot of cities practice TNR, which is trap, neuter release programs. And people who are opposed to that point out that these cats are still outside. They're still releasing toxo and they're still killing birds and endangered reptiles and mammals. It's interesting because I like hadn't, I mean, I knew how big of a problem cats were for wildlife and things. And trap, neuter release for cats that, like, you know are not going to get a home if you try.

and adopt them out because they're feral cats. Like they're not going to tolerate or no one would want to adopt them. It's like, oh, yeah, trapneed release. At least they're not going to be making more cats. But then when you think about when I started reading about toxo and just how much of an impact a single cat can have, like, oh, man, it's rough. It's really rough. And, you know, trapneuter release is meant. to reduce the population of feral cats, it does not work.

Because you would have to, like, if your goal was simply to reduce population of feral and stray cats, trap neuter release doesn't work. Like there are just, it's too effortful for the number of cats that you actually can capture. There's too many cats out there that aren't being captured. Yes. So, but, you know, euthanasia doesn't work either. estimates suggest that only if 97% of all feral cats in an area are euthanized will population numbers actually go down permanently. Whoa.

Cats are very effective at they're breeding like rabbits, I guess. Wow. And so this debate continues to go on over which practice is better or which practice is more humane. But the conversation is starting to shift a little. bit because people are realizing maybe it's not this versus this cats we just have to accept that cats are part of the environment so what do we do about it that's maybe the more pressing issue and that's not something that I'm going to attempt to answer I just simply kind of wanted to bring this up because I think it's a really important bit of information about the problem of outdoor cats and I think

it's an interesting example of how conservation public health and animal rights can all be at odds one another. Yeah. There's no easy answer. There's no easy solution here. Well, at least you can keep your own cat indoors. That's an easy solution. Yes. Yeah. Okay. So you talked about some of the negative effects of toxo in humans, but toxo also can really devastate other animals. Yeah. Sometimes leading to, or often leading to fatal infections. So this is the case, for example, with kangaroos. Kangaroos? Oh, yeah.

It's a big problem in kangaroos. It's also the case for sea otters, which I know is your favorite animal. I know. It's toxo in sea otters is so sad. It's so sad. And the fatal outcome in sea otters isn't necessarily just the direct effects of the parasite, but also the behavior alteration. So we know that toxo can affect the behavior of rodents infected with the parasite.

and we've hinted at the subtle behavioral effects on humans, but it turns out that sea otters that are infected with toxo are three times more likely than their uninfected counterparts to be killed by a great white shark. Whoa! That is really fascinating. I was also reading that it's probably an underestimate how many otters die from toxo too,

just because we only see the ones that wash up on shore and not all of them obviously wash up on shore and things. And the prevalence is like something like 36 to 40 something percent in some populations. Yeah. Which brings me to the possible effects of toxo on humans. Yeah, let's talk about it. So toxo in humans is very interesting and sort of, it's both a budding field and controversial. Yes.

There have been many different studies that have tried to associate toxoplasmosis infection with increased risk of car accidents, suicidal tendencies, just overall attitude or personality changes. And the results are, like, there are some compelling results, but a lot of them seem a bit difficult to disentangle, like not everything has been controlled. And it's like a very, it's just hinting that there might be something going on there. Not enough to, I think, say, this is conclusively showing an effect. Definitely don't have any solid. Right. But the big one that has made the rounds is the association with schizophrenia. So basically what proponents of this hypothesis believe or suggest that infection with toxoplasmosis leads to an increased risk of being diagnosed with schizophrenia. So let's go through some of the

evidence and support of this. One thing that a lot of people say or that a lot of people point to is that there don't seem to be descriptions of schizophrenia prior to the 1800s, and that's sort of when cat ownership really came into fashion. There's also the seasonality of schizophrenia. So people diagnosed with schizophrenia tend to be born in winter and early spring, which means that during the time their mom was pregnant, an outdoor cat might be spending more time indoors. But I also don't know if they looked at people from both hemispheres, and if they controlled for that, and then whether it's like latitude alone. Yeah.

Huh. Okay. Another piece of compelling evidence is that people with toxo, and this is sort of like the bottom line evidence. Okay. People with toxo are three times more likely than uninfected people to be diagnosed with schizophrenia. Okay.

But at the same time, the vast, vast majority of people with toxoplasmosis have not been diagnosed with schizophrenia. Right. And there are people who have schizophrenia who have been diagnosed with schizophrenia and do not have toxo. So. So, so then they suggest maybe it's more of a predisposition or susceptibility thing. Yeah. And also compellingly, the some antipsychotic medicines that are used for people who have been diagnosed as schizophrenia do seem to be effective in stopping the progress of at least one stage of the parasite. I think that that is very, very interesting. Yes. But does not mean that toxo

causes. No. Yeah. Let's look at the other side of the evidence. Okay. Because this has gotten a lot of popular science press. Yeah. And I think it just is like weighing the evidence is important.

Yes. Okay. So there are huge geographic differences in toxoplasmoses prevalence. And some countries have prevalence rates of 90%. Yep. And others are, others are much lower, like 10%, 20%, which is still really high. But anyway. But the core.

corresponding rates of schizophrenia diagnoses don't match with these. Okay. So the places where you find the most toxo, you don't necessarily find higher rates of schizophrenia diagnoses. Okay. And even looking within a country, you don't see a drop in schizophrenia diagnoses following a drop in toxo due to increased food hygiene standards or something. And the other thing is that these are all correlation studies.

Yeah. So we don't know what came first. Was it toxo or schizophrenia? Could it be that someone who has been diagnosed with schizophrenia is more likely to get toxo than someone who is not? Like, you know, these are correlation studies. And so some researchers have criticized these tentative links between toxo and schizophrenia as building false hope. Once the public, though, got wind of the possibility that infection with this parasite could alter human behavior, the headlines have gotten just a bit more bizarre and some of them pretty crissue. or eye rolling.

Yeah. There's an opinion piece suggested that the Brazilian soccer team was so good because high rates of infection led to increased risk-taking and aggression. Oh, my gracious. Yeah.

So, or maybe Toxo did shape civilization itself. Who knows? You know, I wanted to talk a little bit about these studies, but mostly to say grain of salt this. So I think I'm ready to get back onto some solid ground, with real numbers. Can we please? Erin, tell me where we stand with Toxo today. Oh, you want me to do that. I do. Okay. We'll take one more quick break. Anyone who works long hours knows the routine.

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Indeed.com slash podcast. Terms and conditions apply. Need to hire? This is a job for Indeed sponsored jobs. All right, so toxoplasmosis today. Like we said already, but it bears repeating, the estimated prevalence in humans of toxoplasma gondiae infection is between 25 and 30% of all humans. 25 and 30% of all of humanity. But like you mentioned, this isn't equitably divided. In some places where, for example, consumption of raw meat is more common, or in tropical areas that are very favorable for that oocyst persistence in the environment, in those areas, seropululence can be as high as 50, 75, or even 90% in some areas.

And in other areas, it's a lot lower. In the U.S., it's estimated around 20%, 22%. Okay. And zero prevalence tends to increase with age, which makes sense because it's kind of just like you're living your life and at some point you'll be exposed. So the older people are, the more time they've had to be exposed. Mm-hmm. But these infections really do have pretty serious consequences.

In the U.S., it's estimated that the annual cost, I know you don't like looking at the numbers, but I mean the dollar numbers. Oh, no, I mean, I think it's important. I think it's just important to keep in mind also that the U.S. cost is going to be very different than other places that have better health services for their population. For sure. But in the U.S., it's estimated that the cost of illness is $3 billion and 11,000 quality-adjusted life years lost. Wow.

Also, did you know that over 2,000 people develop eye disease from toxoplasma in the U.S. every year? But, and here is something I absolutely did not realize. Toxoplasma gondi is one of the three salmonella, Listeria, and Tegondii. These three pathogens account for over 75% of all deaths due to foodborne illness in the United States. Whoa. Yeah. Whoa. Right? It's estimated that toxoplasma in 2011, I believe, caused 8% of hospitalizations and 24% of deaths from foodborne illness. So, why don't we hear about this more? Why don't we hear about this?

We hear about this, you know, bananas, tenuous at best links with schizophrenia. And we don't hear about people dying from toxoplasma infected meat or food. Hold on. Are these associated with particular, is this like an outbreak or are these individual cases? No, individual cases. So we don't really which probably explains why they're not as headline worthy. For sure, for sure, for sure. Yeah. Now, that's in humans. It's not only in humans. It's not only in mice and rats and it's not only in cats. Over 300 species of animal can be infected that we know of. with Tegondi. Hugely important is the fact that because these oocysts persist in the environment,

they can get into the soils and the water and end up, like you mentioned, in our oceans. Did you know that in Morrow Bay alone? Morrow Bay is in Northern California, by the way. Yeah. Okay. In Morrow Bay alone, domestic cats deposited 77 tons of poop. That's not including free-roaming cats,

which deposited another 30 tons of poop. That means 4,500 little parasites oocysts per square meter. It's really hard to even fathom. Yep. Because these cats, so infection in cats is generally asymptomatic. Cats are the definitive host for the parasite. The parasite doesn't cause illness in cats very often at all. But cats shed this parasite for up to three weeks at a time when they get infected,

and they're shedding thousands and thousands of these parasites every time they poop. So it really does have a huge impact on wildlife and other animal populations across the globe. It's a pretty big conservation and public health problem. Yeah. So one of the things that's really interesting is that there's a big push to look at toxoplasmosis from a one health perspective, which we've talked very briefly about One Health on this podcast before. But essentially, One Health is just this idea that animal health, wildlife, domestic animal,

and environmental health all play into each other. So looking at disease from all of these different aspects and trying to get a handle on understanding the risks of disease from an interdisciplinary perspective is really important for control, not just for humans, but for the entirety of wildlife, domestic animals, and the environment. So for toxoplasmosis, that means trying to get a better handle on the risks from the environmental perspective. so soil studies, land use effects, also a better understanding of the potential effects on human behavior, tenuous though they may be. Understanding the extent of congenital transmission, it's estimated that there are anywhere from 400 to 4,000 cases of congenital toxoplasmosis in the U.S. alone every year. Wow, and we have a relatively low prevalence rate compared to other countries.

Yeah, we really do. And this is not a reportable illness. Is congenital toxo reportable? It is not a nationally reportable disease. Wow. Which means we don't really have a good handle. That's why the estimates are anywhere from 400 to 4,000 cases. Makes sense, I guess.

But then also understanding the wildlife and domestic animal cycles, food safety is really important in talking about toxoplasmosis. And then, like you mentioned, outdoor cat monitoring and control efforts. And of course, vaccine development. There is actually a vaccine for sheep that's licensed in some countries. Yeah. But there isn't even a vaccine for cats, which is kind of bonkers to me. There was one that was made at some point, but it was very expensive to produce. It was difficult to keep. It had a very short shelf life. And cat owners didn't care about it, probably because it doesn't generally affect cats negatively. So it was discontinued by the manufacturers. Huh. Yeah. Interesting. So that sucks. Yeah. It does seem that sort of the biggest ways that you're likely to be infected are from contaminated meat sources.

So cooking your meat properly is important. But also, the oocyst can persist in the environment. So contaminated water is a huge issue. The oocyst actually are viable. They're not killed by chemical and physical treatments that we use for water treatment, including chlorination and ozone treatment. Yeah. And they can survive freezing and pretty high water temperatures.

So, wow, wow. Cool. Cool. Yeah. So toxo is pretty much everywhere. again, the vast majority of humans who get infected will never, ever know that they were infected. But for people who are immunocompromised or for pregnant people who get infected the first time, the effects can be very devastating. Yeah, it kind of remains this vague threat.

Yeah, it does. And then for wildlife species, it can be really damaging as well. So it's a really happy ending. That's pretty much. Yeah. Aaron, tell us about your sources. I read a couple of books. One I already mentioned called The Lion in the Living Room by Abigail Tucker. This is a very fun read. I recommend it. And then another book by Catherine McAuliffe called This Is Your Brain on Parasites. And that's another fun read as well. And then I read a bunch of different articles mostly by J.P. Dubet. He's like, yeah, I read some by him too. It's awesome. Yeah. Tons and tons of history research.

Yeah. Yeah. And one of the books, yeah. And where I got all the information or a lot of the information about sort of of the human evolution and agricultural settlements was from a paper by Schwab at all from 2018. It was great. Awesome. We'll post all of our sources for this episode and all of our episodes on our website.

This podcast will kill you.com under the episodes tab. Thank you to Bloodmobile. for providing the music for this episode and all of our episodes. Thank you all for listening and for keeping your cats indoors safely with you. And with that, wash your hands. You filthy animals. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy.

Sounds great, but a lot of these quote-unquote fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies, just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies, 100% human grade, real ingredients, beef, sweet potatoes, green beans, delicious. These are foods that you would want to eat, not that the babies would ever share. Just food for dogs is the number one bet recommended fresh dog food, backed by over a decade of research, no marketing fluff. My dogs lose their minds at dinner. They run to the bowl, tags wagging, paws tapping, full Broadway performance every single night. So I do care about the food I feed big and smalls.

So go to just food for dogs.com for 50% off your first box. No code, no gimmicks, just real fresh food. Truck month is going on now at your local RAM dealer. Hurry in for great deals and exceptional offers on a powerful selection of RAM trucks. And right now purchase and get zero percent financing for 60 months on 2026 RAM 500 Big Horn and Laramie models. Don't miss this great offer. See your local RAM dealer. Not compatible with any other offers.

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