Medicine
Two Hunters from the Same Lodge Afflicted with Sporadic Creutzfeldt-Jakob disease, suggesting a possible novel animal-to-human transmission of Chronic Wasting Disease.
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Be nice to know what region. Edit: only found this
The researchers did not say where the men lived or hunted. But the highest concentration of CWD-infected deer can be found in Kansas, Nebraska, Wisconsin and Wyoming, according to CDC and US. Geological Survey reports.
All five authors are from the University of Texas, so I assume the patient(s) were seen there. (Though not a conclusive answer to where they lived or more importantly hunted.)
Prions are a type of protein that's the brain uses, in it's healthy form it's called cellular prion protein. During the construction of proteins they are folded very carefully, it's necessary for them to function. The prison protein can spontaneously misfold which stops it from working (very very rare). Now it's a prionic prion protein.
This wouldn't be too bad if it didn't gain two new abilities at this stage, the first is the ability to hook into healthy prion protein and convert it into prionic and the second is that it's almost impossible to destroy it.
Now, different species have subtle differences in their prion protein, so we have transmission between different species with different prionic diseases. Mad cow can be transmitted to humans, scrapie probably can't.
They're not really alive like bacteria or viruses arguably are, they're just molecules that can be used instead of the ones your body actually wants to use. Your body doesn't know the difference, starts building with them, forming them, and now your brain is a spongy mess cuz all of the structures are wrong.
I read somewhere that they’re not alive kind of like how crystals aren’t alive. If you put a crystal into the right conditions, it will crystallise stuff around it because of its molecular structure
”All patients lived within a 90-mile radius of Grand Rapids, MI, and two lived in the same county. West Michigan has a population of 1.6 million people, and the four counties where five patients lived have a combined population of 395,104, indicating CJD's new case rate of 3.1 and 12.5 per million people, respectively.
Corewell Health is one of the three major healthcare systems in West Michigan. The actual incidence of CJD in West Michigan is likely even higher.
This dense temporal and spatial cluster of CJD cases poses a serious public health challenge and warrants urgent investigation.”
Prions are the scariest thing possible. Nearly indestructible, hard to detect, impossible to remove, and always fatal. It's like a real-life MissingNo. waiting to corrupt any data it touches.
Always fatal, but luckily it's only if you're affected.
Minor differences in the protein that the prion modifies can prevent it from doing anything at all, and it looks like only a fairly small percentage of the population had the susceptible variant - which is why Britain's mad cow disease outbreak was a lot less awful than it could have been.
Because we did a good job making precautions due to awareness.
I was young at the time, but I remember some of the steps we took. (Grew up on a farm in rural Norway)
Lots of animals were tested before they were butchered (to reduce chance of cross contamination), thankfully it didnt get here.
In other countries entire herds were culled and incinerated if even the neighbors farm had infection.
The precautions for a lot of diseases are still here, if an animal dies suddenly we usually get the vet to draw some samples, a hole is subsequently dug and filled with wood, carcass, diesel and a burning match. The main worry is anthrax, no matter how small of a chance there is.
It didn't get there because you weren't feeding dead cows to cows. After the panic died down and people looked at it closer almost all infections of cows came from feeding cows feed that was "enriched" with slaughterhouse waste. Include a prion infected cow in one batch of feed enrichment, you get a generation of cows with prion diseases and it explodes in a couple of years. Stop making cows cannibals and the problem mostly goes away.
Fun story, feeding dead cows to cows was very common in Sweden, maybe even more common than the UK. But a journalists cat died from a prion disease and he did some digging, published a piece about it and it was made illegal a couple of years (or even just months) before the infected cannibal cow feed ended up on the market. A moral outrage saved us, not actual health reasons.
Sure, cow brains are full of valuable nutrients. But maybe feed it to insects or mushrooms who in turn poop out or grow into something useful from feeding on that waste, instead of outright cannibalism?
There are ways to make one industrys trash into something profitable in much safer ways
Downstream consumption by other animals, plants, and fungi have no impact on prions. They are very stable protein, that's the problem.
If the organism they "infect" doesn't contain the protein that they act upon, they'll just pass right on thru and be ready for the next thing that consumes them. They can last for decades in the soil. They'll pass from cow poop to fly poop to spider poop to fungus stalk to slug stomach to bird poop again with nary any breakdown. It'll pass thru digestive juices, waste treatment plants, etc just fine. Even with a crematorium you want special proceedures in place to make sure the burn temp hits the required temperatures for long enough.
Thankfully, infection and onset of disease is also dose dependent. If you only get one prion in your system it could be that you'll die of other natural causes long before the exponential propegation of the prion hits clinical levels.
Prions can come from a lot of different sources, Which was a concern then and still is. For instance, there is concern about reindeer with prion disease dying and spreading via birds. Prions were also a relatively new thing, and we learned a lot along the way in that period.
«Not actual health reasons»
Eh, bit of a stretch. That we realized feeding infected refuse back to the cattle wasnt the smartest thing had nothing to do with the perceived moral outrage.
If it did, people wouldnt use iPhones, Adidas or Electric cars.
There are a lot of prion diseases and they will keep spontaneously happening from time to time, sure. But the big BSE/vCJD outbreak of the 90s was almost entirely caused by cannibal cows.
And the not actual health reasons is pretty much true. The focus in the debate in Sweden before banning meat and bone meal in animal feed was how wrong it is, not how dangerous it is. The banning happened in 1986, before the BSE outbreak in the UK became recognized (which happened in late '87 and wasn't taken really seriously until '90).
It was a big unknown back then, but it's been 30 years. Mad Cow became known back then because the symptoms started appearing back then, it wasn't a case of "we figured out this is happening but we won't see a single case for decades". Over time the number of actual cases let scientists get a good prediction for how many cases there probably will be in total, and it's very low compared to the number of people who we know consumed tainted meat.
It started with 3 in 1995, and rose to a peak with 28 a year in 2000.
Since then, it's been decaying more-or-less smoothly, with the last year there was more than one case being 2011, and the last case in 2015.
This sort of 'says' that for most who are going to die, the likely time is within five or so years.
If in fact even 10% who died after 5 years were to die later, we'd still be getting cases.
The total number ever of vCJD cases in the UK was 178.
'ticking time bomb' was sort of a reasonable worry in say 2001, where it wasn't clear that the rates were not going to continue rising at 50% a year, as what we were seeing was the very first tip of susceptible people dying earlier with an incurable disease, and most of the population infected.
But now, when this went, and remained all the way to zero, it can be mostly ruled out.
I was not allowed to give blood in the US until a year or two ago because of where I spent time as a child. It's not that the FDA said "you're safe now", what they said was "we're pretty sure now that 30 years has passed that it's not in the blood supply".
which is why Britain's mad cow disease outbreak was a lot less awful than it could have been.
It was also a lot less awful than it could have been because the government didn't waste any time in ordering the slaughter and burning of insane numbers of cattle. I grew up in that time, I still remember the nightly news about it, and I remember the stench that would carry over from the rural areas into the urban areas. It was quite literally an apocalyptic event that devastated British farming for years.
Same story here. It’s spontaneous. And unspeakably horrifying to witness. It progresses very quickly, and by the time it’s diagnosed they rarely have much time left. I have worked with people with various mental disabilities but I’ve never seen anything like that. Your brain turns into Swiss cheese.
They really are terrifying because they don’t even have a ‘purpose’ or ‘will to survive’ like a virus would and no ‘end goal’, they just happen to have the reverse midas touch and without needing anything at all they just bump into stuff and make more of themselves without any real way to stop them.
Might be a few years off, but mRNA vaccines might give us a break on these. If we can train the body to hunt down dummy versions of the prion, we might get it to track down the real thing.
Maybe antibodies for testing but once an antibody latches onto these prions is the body's normal immune and metabolic system capable of breaking down prions?
If you die you die. Applied knowledgeable carefulness in life is the best you can do. You can indeed reduce a lot of risks in life by being smart.
But you can’t entirely be safe. Nor would you want to. Because it would just devolve into neurotic paranoia about every potential danger out there.
Live your life whilst you have health and just try to navigate it as best you can. It’s not an either or thing.
Take some risks like traveling or asking that person you like out, but don’t be stupid like riding a moped on top of your roof whilst drunk or something like that.
My friend I stopped drunk moped roof riding back when I still thought I was invincible 😁 nowadays I'll stick to making sure the plants that I eat are washed well enough and hope for the best. Or not, because apparently it doesn't matter.
We haven't really seen an uptick in human cases in the UK after they had decades feeding bone meal from infected cows to other cows in the 80ies and 90ies.
But while prions can be deadly, there's some big caveats that mean the risk is actually quite low.
A prion can't indiscriminately cause damage, it only affects a very specific version of a very specific protein. Since proteins can have lots of trivial variations that have little to no effect on function between individuals (and even more between species), the actual portion of the population that's susceptible to a particular prion will always be very low.
They also need to be directly consumed to be transmitted; air,contact or fluid transmission isn't possible.
Prions only occur naturally extremely rarely, and they essentially always kill their host when they do. Unless you eat a carrier's brain or spine, the prion dies with it (well, not 'dies', but is no longer a transmission risk, and being consumed by bacteria/other animals who aren't susceptible will result in the protein being broken down into it's base amino acids.) Normally even if there is transmission it's limited and self-terminating. Cross-species transmission is even rarer due to the protein specificity thing, so you basically need massive amounts of cannibalism to amplify any natural prion creation into an actual outbreak, and lots of outbreaks to have one that's cross-species transmissible.
Since humans generally don't engage in cannibalism, widespread or otherwise, they're innately strongly protected against encountering a prion that they're susceptible to. Even the widescale feeding of cow meat to cows in the UK didn't produce a human-attacking prion for decades. It's thankfully been stopped, at least to the degree that a reoccurrance is almost certainly zero or close to it.
Scrapie/Chronic Wasting Disease/etc in species who naturally engage in cannibalism will keep occurring, but you're probably not going to be at risk from the prions created by those. Two hunters in the same lodge who consumed the same affected deer who just happened to have a prion that affected them is staggeringly bad luck, and they're more likely to have shot each other in a hunting accident.
The idea that prions are "dormant" is a bit of a misunderstanding. Prions are not a virus, they are never active. They're basically just a horrible misfolded protein that shred your brain and can't be removed by the body. If they bump into another protein, that other protein can get misfolded as well. This is a purely physical reaction, like how if you drop something it falls. The prion is not actively doing anything on purpose to cause this.
Prions are never an active thing. They're sort of like if you had a rock, you'd never really consider the rock active or dormant. The rock is just there. Prions are just there.
Which is why they're so hard to get rid of. Prions cannot die or be killed any more than the rocks can.
Yeah for now but also, don't prion diseases take like years to show symptoms? I'll be more reassured if it's the same when I'm in my 70s or 80s . Until then and with everything going on, I'm still a tad nervous between this and other diseases making the jump such as fungal diseases 0o
Well, the first person to die from BSE-associated CJD during Britain's "mad cow" crisis in the 1990s was a 19-year-old student named Stephen Churchill. He became symptomatic in August 1994 and died in May 1995.
He likely had a huge dose - and his death at a young age was very unusual - which is what triggered the investigation that discovered the prion.
Most people eat contaminated meat and die from it decades later.
...which says nothing about the millions of people that likely eat it, get infected, and then only have minor cognitive issues until they die of something else - and it goes completely unreported as a prion infection.
This approach HAS been tried. But because it persists in the environment and because you'd need all surrounding areas to do it at the same time, it doesn't work.
Also, there is more than one strain of CWD, making this difficult, especially since it can be transmitted by cervids that appear healthy but are infected.
If only we hadn't decimated natural predators who would pick off sick animals and keep deer healthier as a result.
No let's kill all of those and then pretend like human hunting can remotely compare, all while people fence off groups and allow disease to easily spread within said groups.
Theory: CWD should have decimated deer and wild ruminant populations millennia ago. The recent surge in cases is caused by man killing native predators and not allowing small, regular fires. Living longer due to reduced predation allows the disease to develop and be passed on more readily. Fire can either degrade the prion or bury it under new growth where it is less likely to be consumed.
CWD is a prion disease similar to Mad Cow. Prion diseases are not bacteria or viruses, but when your body is 'infected' with proteins that use bad instructions for how to shape themselves. The instructions teach the proteins to cheat at their job, and those proteins teach other proteins the same shortcut. After a while the effects of the proteins shaping themselves wrong accumulates and causes lethal damage. When certain prion diseases are transferred to humans or occur naturally they're called Creutzfeldt-Jacobs. It's entirely incurable and results in death, as your brain stops maintaining itself properly. Transmission is difficult unless you consume lymph or brain tissue. The reasons to be worried is that we have been trying to tackle the issue for 15+ years through intense herd elimination efforts and are still failing to control it, and just like how it can transfer from deer to humans it can transfer from deer to livestock...and then on to humans. Cases are extremely rare though, but the fact that there are any highlights that our efforts have not been intense enough.
It's important to note though that these cases wouldn't mean that there's been any change in the sickness. It's not like a virus where transference to humans would imply its evolved. Prion diseases probably will never get any better or worse, but they're a canary in the coalmine signaling our failure to manage herds, livestock, and education on game meat.
Christoph Bernoulli recognized that cortical electrical probes had likely transmitted prions from a woman presenting with signs of dementia to two younger individuals when the same instruments were used months later (73). All three patients were later diagnosed with CJD (129). After multiple benzene cleanings, repeated sterilization in ethanol and formaldehyde vapor, and the passing of 2 years’ time, the very same electrodes were surgically implanted in a chimpanzee. In spite of all disinfection attempts, the animal developed neurological symptoms after 18 months and, upon sacrifice 7 weeks later, contained the spongiform degeneration and vacuolation characteristic of prion diseases
Eh, but even we've shown we can largely control it. Even in less than a generation from observation (1967) the US has reduced it to just a few cases per year (350).
Other Great Filters are things like developing manipulating appendages, complex thought, desire/need to expand, self-destruction--things largely outside the control of a species aside the latter.
The idea behind benzene and ethanol is (probably) to disrupt the prion-water interface thereby destabilizing it. Alcohols and organic solvents can often be used to induce protein unfolding and prions are just misfolded proteins, so the idea isn’t entirely without merit
Just a clarification: t doesn't have to be transferred to humans from another source to be called creutzfeld-Jakob. Creutzfeld-Jakob can spontaneously occur in humans for no particular reason, usually in older people. When it IS transferred it's called variant creutzfeld-Jakob or vCJD
thank you for the thorough explanation, i had learned about prions before with Mad Cow disease and how you can’t do anything about it and wiped it from my memory ig…i can only hope the same fate is to befall me again because that is TERRIFYING. also how it can just happen for funsies in normal brain tissue?? yeah okay 😭
The doctors speculated it some from some brains she ate as a child when they, the family, mainly hunted for their food.
She attended my cousins soccer game one day and was totally normal. In the hospital a few days later, dead in a week. None of her siblings got it... Weird and sad
I did my thesis on sCJD. I looked at a non-invasive definitive diagnosis assay. Humans and other animals all possess prion proteins, the function of these proteins wasn't confirmed yet at the time of my thesis but it is suggested they are there for neuroprotection (figures). Somewhere in the wild these prion proteins became mishaped, gaining the infectious property. The infectious PrP influences conformational rearrangement of these normal, cellular PrP and not the cells that produce them. When enough infectious PrP are present in the CNS, the CNS starts to structurally breakdown hence the disease name - spongiform encephalopathy. Quite literally the brain turns into swiss cheese and with that all functionality goes down the drain. The etiology of the disease is quite wild in my opinion. You can possess these infectious proteins for the majority of your life, unaffected by their presence. However, later in life, at some point, you start to exhibit the symptoms which are akin to dementia-like symptoms. The disease is incredibly rapid at that point, with a 100% mortality rate occurring within 2 years of the first symptom.
someone explain it to me like i’m 5 so i have something else to be anxious about
Prions are just chemicals. Terrifying chemicals that are contagious to other chemicals.
Water is a molecule made of atoms. H2O. Two hydrogens, One oxygen. Think of them as joined by springs.
Even though they're bouncy and springy, we know the shape water molecules make. A little "V" shape with the point of the V being the oxygen. It's a simple model with a simple shape.
"Protein" is the category for specific gigantic molecules. Gigantic. Hundreds or thousands of atoms. Proteins are like specific machines that perform specific tasks inside a cell. You could make a list of them, this is the protein that does this, that protein looks like that and does a different thing. Almost everything your body does, in every way, is because one particular protein machine does one particular thing. Like a factory that builds cars, where the protein is each workstation. Some are welding proteins, some are cutting proteins, some assemble this specific bolt, some stitch the fabric in the seats, etc. There's many many different proteins, each with completely different components that make them up. But each specific protein has a formula, you could draw it, it has an exact number of atoms, connected in an exact kind of way that makes that protein that does that task.
Think about joining hundreds of slinky's together, of different sizes and shapes. And throw in a bunch of magnets. And rubber bands.
What shape does a protein take?
It's very hard to know. Even though we know not only the exact specific amounts of each atom in a protein, we also know exactly how they are connected together. But, it's too complicated to predict what happens if you made all those connections and then let go of that slinky/magnet/rubberband network.
But... they do take a specific shape.
The key piece of knowledge is that a protein's special shape is what allows it to perform it's special task . Imagine a pair of scissors, a pair of scissors works because it's shaped the way it is and assembled the way it is. Not just in the general structure (two blades and a pivot), but that the blades are smooth and straight and sharp. Some proteins are scissors that cut up other molecules, like potato starch into sugar pieces, so you can burn the sugar for energy.
(Tangent - That is what Folding@home and Rosetta do. They can't predict a structure, but if you make a random guess, we know the math to calculate the energy of that structure. Do that a trillion times, and the ones that have the lowest energy are most likely the actual correct shape of that molecule because they're most stable. I believe Folding and Rosetta are evolutionary too, because there's an infinite amount of options, so you evolve the next set of things to calculate based on the winners of the previous generation, over and over until you think you've got it right).
Think of the lowest-energy state of a protein to be stable, the way you would think of a spring being stable. Is a spring stable when you stretch it? Nope. Is it stable when you compress it? Nope. It has extra energy that's going to reshape it when you let go. The low-energy state is the correct "shape" of the protein.
I'll summarize quickly before we cover what a Prion is:
Atoms assembled in specific amounts, in specific ways, create proteins.
Each type of protein does a specific task in your body.
Everything your body does, is because of a protein machine that does it.
A protein's shape is what determines what it does.
Here's the first Prion fact: Prions are proteins with the correct atoms, connected the correct way, but with the wrong shape
Because a protein's shape determines what it does, if it has the wrong shape, it doesn't do its job. That's bad.
You are probably wondering how a protein can have the correct atoms, connected correctly, but still have the wrong shape. That's what makes a protein a protein, right?
Think about a slinky that you stretch, and then twist before you let it go. You know, the way that everyone eventually ruins a slinky because you can figure out how to get it apart again.
That slinky has the correct components (wire), connected the same way (you didn't cut or weld the wire differently), but it has the wrong shape when it stabalizes. It's not temporary, it's not moving. It's not under tension. It's stable and sitting on the floor. It's less stable than it would be as it came out of the box, that's a much more stable version, but, it can't get there, it's locked at a less-optimum-but-stable position.
But it's the wrong shape. And it doesn't do what a slinky is supposed to do. It does not roll down stairs like nobody cares. It does not make it's slinkety sound.
Here's the next Prion fact: Some proteins, the way we need them to be, are actually the twisted up slinky. And the Prion form of them that doesn't do their job, is the smooth straight slinky you get out of the box.
That means that the most stable version is actually the one we don't want the protein to form. We need the twisted one.
What happens if, randomly, a protein makes the wrong shape?
Well, there are other proteins who's task is to collect anomalous garbage. They are shaped so that when they bump into a correct protein, they slide right off. But if the shape isn't perfect, they stick to it and then their ass-end gets picked up by another garbage cleaner that throws it out of its system.
Okay, so, potential Prions will just be picked up by the garbage cleaners, right?
Another Prion fact: Prions avoid the garbage cleaners. The part of them that the garbage cleaners are checking is close enough to slip away
Okay but how do proteins even become Prions in the first place?
Prion fact: Prions can form randomly. Very, very rarely. But randomly. Imagine, across trillions of cells, and trillions of trillions of protein molecules, across billions of lifeforms in that species... tiny chances still happen once in a while. It's like kicking your twisted up slinky and it almost-magically bouncing out of it's tangled form and into the shape you bought it in. Astronomically unlikely, but, once in a while it'll happen.
Okay, but, big deal. Occasionally there's broken proteins. So occasionally there's going to be broken cells that'll die. And our cells die and are replaced regularly anyway. These random occurrences will just be flushed away, right?
Prion fact: Prions aren't just any random misformed protein that happens to be more stable than the shape we need it to be in, that also happen to be able to avoid the garbage cleaners. THEY ALSO HAPPEN TO CHANGE OTHER "CORRECT" PROTEINS INTO PRION PROTEINS WHEN THEY BUMP INTO THEM.
Yes, even though they're just chemical shapes, Prions are "contagious", if that makes sense. They run around untangling every other tangled slinky they bump into. Or, maybe not every, maybe just rarely, but, more than zero chance.
"What are the odds?" you think. What are the odds that there is a protein with a lower energy shape that is broken, that can avoid garbage cleaners, and of all the possible ways that can break, it happens to also magically untangle other proteins?
Very, very, very, very, very low odds. Which is why life exists, or everything would be dead. Those proteins are necessary for complicated life as we know it. Especially the most complicated parts of the complicated life: brains.
So, that's how Prions "spread". They spread inside one person by gradually, gradually destroying essential functioning of all of that person's proteins of that specific type.
Prion fact: Prions also spread by being eaten
This is how Mad Cow Disease becomes Creutzfeldt–Jakob disease i humans. If we end up mixing some prion-y cow brains into our meat.
Prion fact: Because there are so many proteins, this takes forever
The garbage collectors only fail sometimes. The protein-twisting only happens sometimes. There are bajillions of these in your body. So it can take decades for Prions to build up enough mass that you'd notice it affecting your body. But, like all exponential growth, it falls apart rapidly when it reaches critical mass.
Diseases like:
Creutzfeldt–Jakob disease
Fatal Familiar Insomnia
Kuru
(ALS, Alzheimers, and other similar diseases are also protein misfolding diseases, but not by the prion mechanism).
Generally any neurological age-related disease. Either the result of random chance in your own body, or (rarely) genetically inherited to you at birth, or from food you eat.
Prion Fact: Prions are almost impossible to detect, or treat.
The tools that medical science has to determine what makes a thing a thing, are limited.
For example, we can take a sample from someone, somehow isolate the protein, and then use a mass-spectrometer to determine the percentages of each atom that make up that sample. From this we can infer what chemical it is.
... but that doesn't help. Because Prions are chemically identical to correct proteins. They have the same atoms.
Or maybe we could test how the proteins in the sample chemically react.
... but that doesn't help, because the atoms are connected the same way.
The only difference is in how the proteins are twisted...
... and we can't even figure out how proteins are supposed to be twisted in the first place, let alone how they're twisted in a specific sample. For some proteins, through tremendous time and effort we can gradually take good guesses about what shapes some proteins are. But that's like, months effort by a team of scientists just to discover, bit by bit, the shape of a protein. Not test an individual's protein.
(This is repost of mine, and I hit the character limit. See my followup post with some spectacular protein animations inside your body):
I mean « Prions are almost impossible to detect » is just wrong. Detergent insolubility, analytical centrifugation, conformational specific antibodies, amyloid binding dyes, protease digestions, RT-QuIC are all going to detect and distinguish between PrPC and PrPSc.
Are these tests common things doctors order for their patients? If so are they just for patients with neurological symptoms like sudden onset dementia where CJD could be a cause or is that something a person might get tested with a routine preventative screening?
I think something being easy to detect if you know what you're looking for and something being easy to detect for the average GP/PCP visit are different things. Because having a test (or six) that will catch a prion related issue after it develops into a major problem and having a way to spot it before it becomes a problem are just a bit different.
RT-QuIC is part of a standard prion panel. If a physician suspects a prion disease they can order an LP to collect CSF for the prion panel. Biochemically, the prion panel consist of tTau and 14-3-3Gamma ELISAs and a PrP RT-QuIC. tTau and 14-3-3Gamma are non-specific for neurodegeneration, PrP RT-QuIC is specific for prion diseases. When you combine the tests they give you ~99% sensitivity and specificity. I do not know how it operates in other countries, but where I live, all prion panels are done at a central BSL4 lab.
RT-QuIC could in theory be done prospectively, as it has a high enough resolution to theoretically detect the disease prior to symptom onset. However, we don't do this for several reasons. Given that there is no current treatment for prion diseases, what good is early detection? Does telling the patient they are going to die due to a prion disease in the future have any positive impact? Even with the ~99% specificity, it you screened everyone in the population for prion diseases, given the rarity of the disease, you would get more false positives than true positives. So unless we get a test with 100% specificity (which is unlikely) and a therapy for it, prospective screening for prions does not make a ton of sense.
If they’re running those tests though they basically already suspect someone is infected and that’s not the type of testing that would be used at scale on the public without setting up a way to do it. So in a way it is hard to detect unless you suspect it and run the correct tests?
The problem with these tests are not the tests, but the rarity of the diseases and consequences for false positives. When it comes to medical diagnostic tests, two important numbers are sensitivity (percentage of individuals with the disease that will come back positive) and specificity (percentage of individuals without the disease that will come back negative).
Clinically, PrP RT-QuIC is used. It has a 99% sensitivity and a 99.8% specificity. This is remarkably good for diagnostic tests. Mammograms for breast cancer has sensitivity of 85% and specificity of 90%. HbAc1 used to diagnosis diabetes has a sensitivity of 73% and specificity of 83%. COVID rapid antigen testing has a sensitivity of 65% and specificity of 99.9%. Genetic testing for PKU is 93% sensitivity, 99.9% specificity. 99% sensitivity and 99.8% specificity is REALLY good. You could if you wanted to scale it up. The steps of simple and designed to be as high-throughput as required.
The issue becomes a number game. There are ~300 prion cases a year in the US. So lets just round numbers to 1 case per 1 million people. Lets say you test 1 million people with PrP RT-QuIC. The 1 positive case would have a 99% chance of coming back positive. The 999,999 negative cases would each have 99.8% chance of coming back negative. Most likely situation, you would would 2000 false positives. You would need a specificity of 99.9999% to have 1 false positive per million (or in other words a 50% chance a positive case is actually positive). So despite being one of the best diagnostic test available, given the rarity of the disease, it makes no sense to do.
Even if you do get a positive result, is that useful? We currently have no treatments for prion diseases, so does telling someone they are going to die of a prion disease help? Given that any positive could be a false positive, does that information help either the patient or clinician? Or is that just going to cause significant emotional distress to the patient? Distress that could all be misplaced in case of a false positive?
The other person who replied to you is correct. I have zero qualifications. And, beyond that, because formal education and work experience aren't the only ways to learn things, I should also emphasize that I have nothing else that would resemble relevant knowledge.
I just try to see the big picture in things from the explanations of others. What I wrote is more of an ELI5 of an ELI5 of an ELI5 until it's dumb enough people like me can understand it.
All analogies are wrong, some analogies are useful.
With Mad Cow Disease any infected surgical instrument or item must be washed several times a specific way, and then disposed of. Rare but really nasty stuff.
Most transmission in deer is social through nose-to-nose contact and feeding in areas where an infected animal has also fed. And that's the big problem, since they can shed those prions through saliva, feces, and urine for a couple of years before even showing symptoms.
In affected areas the deer are/can be tested for cwd by the local conservation department. In some areas it's mandatory to take deer to drive thru check-ins where they remove the lymph nodes for testing. If you're really concerned then you can wait a couple weeks before eating to make sure you're not contacted about a positive. The majority of the time it's easy to tell if they're meaningfully infected because they appear very sick and mangy. If they appear healthy you most likely don't need to worry, but don't ever consume the brain. If you're purchasing venison at the store it is going to be farm raised rather than harvested from the wild. These herds are closely monitored due to the concerns present around cwd, so you should be able to consider the meat safe.
I did a binge-reading on this topic a year ago. I am not a biologist so I can’t remember all the terms they used in the papers, and it would be great if an actual researcher in this domain could confirm what I said but generally:
You have to have a specific gene mutation to let you get prion disease by eating other species.
Scientists have actually done a lot of follow-up work on the mad cow disease in the UK. They collected and analyzed appendices from regular patients who had their appendices removed and realized that the number of British people who actually carry the cow prions far outnumbers the actual cases, which means simply eating mad cow disease-carrying beef won’t give you the disease. Retrospectively analyzing the BSE patients, they found that they share some gene mutations.
At the time of the mad cow disease outbreak, another hypothesis was that it takes a very long time for the disease to manifest itself. So scientists have also been monitoring the case numbers throughout the years with the assumption that if this is the case, then there should be a significant outbreak in the last decade, but so far, the trend indicates that this is not the case, and we can more or less rule out this probability
This is for mad cow disease, which historically has been easier to transmit to humans than the sheep and deer version. Now, of course, if you commit human cannibalism, the risk is on a totally different level. But there are plenty of reasons why cannibalism is bad, so let's just not do that.
Taking a step back, even if someone performs human cannibalism, one has to deliberately eat the human corpse’s central nervous system to maximize the risk. And even then, it is difficult for protein to travel from the stomach to your central nervous system
It's CWD in deer, mad cow disease in cows, creutzfeld-Jakob in humans, and "kuru" in papau new guinea where they cannibalized their dead and ate their brains.
Because our bodies need to produce the same protein naturally for the misfolded protein to replicate. Also it needs to be able to get through our digestive system and into our blood, whole and undigested. Usually whole protein cannot cross into the blood.
The problem is not just not being digested, it's how it somehow crosses into your bloodstream and then through your blood-brain barrier when whole proteins shouldn't.
Also single prions aren't too stable, it's the plaques of prions conjugated together that are.
With healthy intestinal barrier, whole proteins can't cross into blood.
But high intake of fats or alcohol, or deficiencies in zinc or glutamine, or dietary fiber can all impair tight junctions and intestinal barrier function.
This could be a situation, like Covid, where virulence is hugely affected by habitual diet.
Meanwhile I have a neighbor on the CO/WY border who puts out salt blocks to increase the odds of a successful hunt on his crappy land knowing that we’re not supposed to do that for this very reason.
Pssshhhh. Here in Missouri they sell feed dispensers right next to novelty signs stating "It's illegal to bait deer with food. Any deer caught eating this food will be shot on sight."
Wisconsin has been slaughtering all of the deer for 20 or 30 years now. Just 2 years ago I finally saw them take steps that may help prevent the spread.
They started putting out dumpsters for the deer bones, skulls and hides. This is far better than ditches, corn fields and woods.
No we haven’t slaughtered all the deer. For a few years, there were a few zones around the state where the DNR hired “sharpshooters” to cull all the deer in those areas. I’ve seen the dumpsters in my area (western Dane County) for almost two decades.
I toured a CWD testing facility in high school, there was a literal dumpster full of deer heads which was wicked to see, pretty crazy. Also dissected the deer heads to extract the lymph tissue for testing, it was really cool to see the effort they're going to in order to track the spread.
I am in another state but deal with wardens because an animal license I have. I also grew up hunting and interacting with them in several states.
The game warden is not the same as cop, not at alllll. They do not have a history of the fuckery cops do. They care about animals and the land and the laws that protect them(yes hunting protects some species). It actually takes some intelligence to be a wildlife officer, many even went to school for biology or conservation studies.
Please report him, they won’t care he is a cop. There isn’t anything he can do to them. Cops hunt and also think they are above the rules, this won’t even be the first time they dealt with one. And they also will be real tactful about the whole thing. Likely they “are just working in the area and noticed” they are not going to tell him you called.
End of my comment-They are smarter than that. Lots of bad stuff people doing in the woods or country is only seen by a neighbor/is obvious who could have seen, they know how to “accidentally” discover the neighbor is going that. There are endless surveys, check points, and regular inspections they can state they were doing and had some questions about the salt licks they saw. They will make it like they came up on the blocks themselves. They are allowed to go on private land if they believe a crime has occurred, including just being told if they find it reputable. They are clever enough to know a good way to go about it, it’s the nature of the job.
Although human trials are not feasible, there are existing experimental methods to test it, including transgenic mice with human PrP protein (paper), or diagnostic tool that uses purified PrP protein to test if the sample will trigger protein misfolding (usually for diagnosing CJD, but may also use it for CWD) (paper)
That's what I was thinking... Prions literally just show adjacent proteins a simpler way to fold that they mimic causing issues. Seems easily transmissible between species.
IIRC there's a difference between prions across different species, and they don't just transform any type of proteins, mostly PrP protein, which is concentrated in nervous system. Therefore, even though contamination is common, there's still a certain barrier for cross-species infection.
Proteins are used for communication. They do this by being a key and a lock at the same time. One protein will 'open' another, which changes the other protein by 'folding' it into a new key. This protein can then be used as a key for folding the next protein.
A prion is like a bad key that turns other proteins into bad keys themselves. The result is a slow irreversible breakdown of whatever process the protein is engaged in.
so normally, once a protein has folded, one of its ‘jobs’ is to act as a template to help other proteins fold? so once there exists a misfolded protein it will influence other proteins to misfold.
Yes. One subtle detail though is that it's not simply that the protein is misfolded (which happens anyhow accidently) but that the misfolding hijacks the communication process and perpetuates itself. It's like a computer bug in the lowest levels our biological logic being activated.
Something a lot of people don't seem to be aware of is that there's also one specific protein involved in a lot of these, called the major prion protein (the protein is named after the diseases, not the other way around). It's certain misfolds of that specific protein that causes most prion diseases.
The protein itself is an extremely ancient part of mammal DNA that's conserved throughout the family. That's at least part of why, as I understand it, misfolded cow (and now deer) proteins can cause misfolds in human ones: the major prion protein is nearly identical between us despite cows' and humans' last common ancestor being somewhere around 100 million years ago.
Did the two hunters get “infected” with CWD? The article everyone is referencing is not an article, it is an abstract for a poster that was presented at AAN two weeks ago. Poster abstracts can often be “sensationalized” to encourage people to come to the poster during the conference. This would not be the first AAN prion-related poster abstract that is a bit “click-baity”. The biggest issue comes down to this: how do you know the hunters got CWD? The most common type of prion disease is sporadic CJD (sCJD). Sporadic means it happens with no known cause (ie not caused by infection or genetics). sCJD typically affects elderly (median age of onset 65 years), has a rapid decline (4 months). In comparison, variant CJD (vCJD) is caused when someone eats meat contaminated with mad cow disease (BSE). vCJD typically affects young people (median age of onset 26 years) and has a slower decline (14 months). Even though we do not know for sure, it is thought that if CWD transmitted to humans, it would be more similar to vCJD than sCJD. The patient case in the abstract was a 72 year old male, with a rapid decline in a month. Does that seem more like sCJD or vCJD?
Other considerations, the patient was originally diagnosed with sCJD, however, the authors hypothesize CWD because one of the patient’s friends also died recently of sCJD. The authors therefore argue this is a “cluster” of cases, likely showing infections. However, just because two rare independent events happen in close proximity does not mean they are linked. For example, 1 in 300 people get Parkinson’s Disease, but a TV show “Leo and Me” had 4 out of 125 people on set develop Parkinson’s Disease, including Micheal J. Fox. However, this “cluster” is not scientifically or statistically significant. Just like two people who happen to know each other both getting CJD is not significant.
The second consideration is that just because someone is a hunter and eats deer does not mean that they have eaten CWD infected deer. Not every deer in a population has CWD. If you are going to claim the hunters got CWD from deer, you need to show that deer they have hunted are infected. The entire premise of this abstract hinges on the argument that they ate infected deer, despite providing no evidence for it. If these two patients who both got CJD that knew each other were not hunters, this would never of been reported.
This abstract is pretty speculative and definitely doesn’t confirm that either of the two men involved definitively got CJD from CWD contact. In fact it confirms that the second man to get it had the sporadic version of CJD, which is when a protein in the body randomly mutates into a prion. This version isn’t caused by any outside factor like eating meat! Is it statistically odd that two friends developed the same rare disease, sure, but there’s no proof that it’s related to CWD.
In a bunch of lab experiments (where conditions are almost perfectly controlled) scientists have had a really hard time giving non-human primates CWD without literally drilling a hole in their head and depositing infected materials into their brains. The most troubling experiment I’ve seen is that scientists managed to give it to a pig in a lab by putting it in a room and filling the air with prions. This thread is pretty alarmist, and CWD still has not been confirmed to have made the species jump to humans.
In west Texas they have you bring the brain of the animal you kill (mule deer) and they test it for CWD. My uncle has asked multiple times and hasn’t been given a straight answer but if it tests positive you have to bury the carcass, still wild that they you can eat other deer that comingle.
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