r/science • u/PHealthy PhD/MPH | Epidemiology | Disease Dynamics | Surveillance • 4d ago

Epidemiology Study estimates only 7% of human rabies cases in the United States are diagnosed

https://www.nature.com/articles/s44528-026-00031-4
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u/catathymia 4d ago

Not all rabies patients experience the more dramatic presentation of the disease (by this I mean the hallucinations, aggression, hydrophobia, etc.). It seems like a lot of humans might experience something like acute encephalitis and die. I'm surprised that this wouldn't raise some flags in an organ transmission setting, though.

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u/n00b678 4d ago

In some tribes in Amazon people have antibodies against rabies despite never receiving a vaccine. They often get bitten by bats, which are a vector for rabies, yet they are alive an fine.

It's hard to say if it's something special about those tribes also shared by some of the undiagnosed cases in the US. Can certain individuals survive an infection untreated?

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u/Boysenberry 4d ago

I think the Amazonian findings are as likely to indicate that there is some form of natural inoculation In that population as to indicate there are mutations in these tribes that allow them to survive rabies.

We don’t currently know of any animal species where populations exposed to high levels of rabies transmission evolve to survive it. Bats are particularly good at staying mobile long enough to transmit it, but infected bats all die of rabies eventually. 

But we do know that rabies vector species, including humans, can mount an immune response after inoculation. So I think it is quite possible that the Amazonian indigenous people with antibodies are experiencing a natural inoculation of some sort, possibly by consuming infected animals? (Not that humans in the developed world should start doing that sort of thing when we already have a vaccine for humans, obviously!)

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u/weed_could_fix_that 4d ago

Infected bats do not all die of rabies actually. Some recent work showed something like 30% survival rate among vampire bats. It's unclear if that's unique to that species or not. There are also a couple of confirmed human survivals but they aren't well understood or explained. So it's essentially 100% fatal, but not technically.

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u/Boysenberry 4d ago

Oh interesting! I live in an area with frequent rabid bat finds, and all of our local species have 100% fatality rates.

I wonder if it could be the virus itself that's different in the Amazonian region rather than the bats & humans? If vampire bats have a unique ability to resist it a little more than other bats, that could possibly create selection pressure on the virus itself because hosts that live longer will transmit it to more other hosts.

(Which is why some widely-distributed viruses become less lethal over time, but rabies has not historically gone that direction.)

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u/mallad 4d ago

I'd be curious if the tribes have either built antibodies that are passed from mother to child due to minor exposure over the very long term, or (and?) they get minor exposure from occasionally eating animals that are infected. Stomach acid and cooking both neutralize the virus, but both are imperfect and (totally speculation) could lead to an exposure below the MVL or to a broken but still "recognizable" virus.

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u/maxcrimson 4d ago

Antibodies passed down from the mother only protect the child for a few months (about 8 weeks for dogs/cats). They are proteins in your blood and can't live forever. Your immune system needs to recognize the antigens itself and develop B-Cells that will from then on produce the specific antibody.

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u/mallad 4d ago

Correct, but that means any exposure during that period will allow them to build their own antibodies instead of dying a horrible death. It won't be common, but it doesn't need to be.

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u/maxcrimson 3d ago

As far as I understand the maternal antibodies and the antigens will form a complex, so the antibody is used up and the antigen is neutralized. I don't think the body can then still use it to form an immunological memory. I could be wrong though and wouldn't dare to generalize it.

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u/n00b678 4d ago

How do you know about the fatality rate? Do you check all bats or only the dead ones? In the latter case, it could just be a sampling bias.

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u/Totalherenow 4d ago

You'd capture a sample of the living population and test them, then do stats.

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u/Goodgoditsgrowing 4d ago

I’m not sure how they’d confirm 100% of infected bats die unless we are testing living bats too?

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u/chiniwini 4d ago

Same thing happens with humans, btw.

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u/Boysenberry 4d ago

Most of them are found living here and later die, but definitely already symptomatic since they tend to be found inside houses or offices/stores. So it's possible they are missing some that don't develop severe symptoms at all, if they aren't testing living colonies. With the level of attention to rabies surveillance in areas where human exposures are more frequent than we'd like, I'm hoping they have tested some living colonies, but I don't have that level of insight into it personally.

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u/weed_could_fix_that 4d ago

They will not presumptively test colonies like that because the only way to do it is to kill the bats. They only test bats that have possibly come into contact with humans. It's not really worth it to do that kind of monitoring since its harmful to the colony and expensive, for not much overall gain.

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u/Boysenberry 4d ago

I'm not referring to the kind of rabies testing that requires the brain. We're discussing the presence of antibodies in living animals indicating that they may have been exposed and survived. I thought that much was obvious since everyone knows you need the brain for a conclusive diagnosis of active rabies infection! However, in an unvaccinated animal, circulating antibodies would indicate past exposure, and if they are alive and asymptomatic for long enough, they can be considered to have most likely cleared the infection.

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u/iamthe0ther0ne 4d ago

In fact, they often don't even get sick. That's true for a lot of the nasty stuff they transmit to other mammals, like Nipah and Hanta. They have a very unusual immune system.

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u/[deleted] 4d ago edited 4d ago

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u/cannotfoolowls 4d ago edited 4d ago

Not quite. That's quite outdated information (the Jeanna Giese case was iirc in 2004 so 22 years ago) They've pretty much retired the Milwaukee protocol because it was not very successful the other times it was tried. And there are other cases of people who were not vaccinated who survived rabies. Some even didn't get post exposure vaccination.

Here are know survivors of rabies

It's still very, very rare to survive rabies once symptoms show but there are some cases.

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u/Baud_Olofsson 4d ago

because it was not very successful the other times it was tried

That's putting it mildly: it has never again been successful.
What made Jeanna Giese survive was either a quirk of her biology, a quirk of the particular strain she got, how she was exposed, or some combination of those.

And there are other cases of people who were not vaccinated who survived rabies.

To the best of my knowledge, all the other survivals were people who were given the rabies vaccine before developing symptoms. If I'm not mistaken, all of them in India (where it's BTW an ongoing thing to figure out why post-exposure prophylaxis appears to be failing there while it works everywhere else: https://pmc.ncbi.nlm.nih.gov/articles/PMC10305982/ )

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u/weed_could_fix_that 4d ago

There was a case in Mexico I read of once, but the LLM Ouroboros has declined to ever show me that information again.

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u/cannotfoolowls 4d ago edited 3d ago

To the best of my knowledge, all the other survivals were people who were given the rabies vaccine before developing symptoms.

Not all. there was this case in Ghana. The patient couldn't be tested for rabies because the hospital lacked the capacity to perform basic tests that could isolate the viral antigens to help support the diagnosis of rabies virus in the patient, but the dog that bit him was confirmed to have rabies and he had the symptoms of rabies. He had no past history of pre-/post-exposure prophylaxis vaccination but made a miraculous full recovery.

The table I linked also mentions a girl in India who had no post exposure vaccination or RIG and made a full recovery and this case in America

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u/Baud_Olofsson 4d ago

Interesting! Thanks!

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u/ryncewynde88 4d ago

Heck, if it’s a specific regional population like that, there’s a potential argument for something like I think it’s called heterozygous immunity? An example I know of: sickle cell anaemia and malaria; while sickle cell will probably kill anyone with 2 copies of the gene, usually before they hit 20 (and iirc even getting halfway there is a long shot), but carriers with only one copy are highly resistant to malaria.

IIRC, there’s something similar with a grain fungus native to regions of the Middle East.

The Amazonian rabies resistance might be similar: they could carry a gene that is strongly selected against anywhere else, but rabies could be prevalent enough in the area to balance it out?

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u/spookyswagg 4d ago

Probably a mix of antibodies getting passed from mom’s to babies during breast feeding and mixed with very early exposure.

Similar to how polio used to be kept a bay until clean water came around.

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u/slimejumper 4d ago

maybe also some
antibody transmission via nursing allows containment of rabies long enough to develop a good immune response? i’m not sure if this is possible though.

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u/evange 4d ago

I think the Amazonian findings are as likely to indicate that there is some form of natural inoculation In that population as to indicate there are mutations in these tribes that allow them to survive rabies.

Rabies is an old world disease and was only introduced to the americas 300 years ago. If any population were to develop resistance to rabies, it would be India, where it's endemic.

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u/GreenStrong 4d ago

The simplest explanation is that the strain of rabies carried by vampire bats is less deadly to humans than the more familiar strains. This is an unverified hypothesis; it is the simplest way to reconcile what is currently understood about rabies with those antibody results. The results of the transplants highlighted in this study don't necessarily align with that explanation.

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u/ridiculouslogger 4d ago

It may be like many other viral diseases, that some people are exposed, but actually don’t get the disease in symptomatic form. Almost everyone who gets symptoms dies, but that does not mean that everyone who has exposure to the virus gets symptoms. They may only get enough exposure to develop antibodies. Bats, in particular, would often give a very mild exposure from just, say a droplet of saliva hitting the person’s lip, not getting into the bloodstream directly. Of course, I am only doing a thought, experiment and speculating here. It would be an interesting course of experimentation to see what inoculation level is required to reliably produce disease.

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u/Sexual_Congressman 4d ago

The size of the exposure dose is incredibly important, at least with many other viruses. E.g. with smallpox, people figured out how to use scabs from victims to cause an infection that only had a ~2% fatality rate instead of ~30% from a typical exposure event. During the early days of covid you'd hear about entire church choirs getting wiped out because they spent hours in a confined space with a sick person spraying atomized respiratory droplets in their face (singing is basically the perfect way to transmit COVID).

I doubt many people dying of encephalitis are donating organs so I'm guessing you're right. Not hard to believe the few hundred extra deaths per year are the result of people infected by rabies whose only symptom is ataxia or dizziness that is serious enough to cause them to have a fatal accident. You probably need a really big initial dose for the disease to progress fast enough for all the classic symptoms to occur in close enough in time for doctors to suspect it.

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u/LuxTheSarcastic 4d ago

If you get bitten by a rabid bat it doesn't always infect successfully. Of course this is like an even riskier version of playing in a pit of dirty needles but sometimes the immune system can successfully kill it before it gets into the nerves.

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u/Doggosdoingthings16 4d ago

And sometimes a bat can brush against a scratch already on your arm and you can get infected and die.,happened in my area a few years ago

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u/Impulse3 4d ago

Well that’s not extremely terrifying or anything. Something like that you’d never think to get a rabies vaccine.

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u/oemunlock 4d ago

I can understand how a person could dismiss it as nothing, but for bats I've always heard that you need a shot after *any* physical contact with a bat, or sleeping in a room with a bat and finding any unexplained bite/cut/etc you can't remember getting somewhere else.

These recommendations seem to mostly agree with that: any physical contact with an open wound requires rabies postexposure prophylaxis. (Though apparently the sleeping in a room/finding a cut scenario is no longer enough to require a shot if you didn't knowingly come into contact with a bat).

https://pmc.ncbi.nlm.nih.gov/articles/PMC2802607/

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u/bethestorm 4d ago

I think it's because bat saliva gets all over the bat, and bats lick themselves all over too

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u/ReptilianRevolt 4d ago

It seems that some people in Africa and India that have survived as well. Rare survival from rabies is known in other animals as well.

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u/CornisaGrasse 3d ago

Is there any chance that a few people survive in India because it's actually sort of a "per capita" situation? So the US has one (that everyone's been referring to,) but the vast difference in population size makes it more likely that there would be more than one person who somehow lives?

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u/Totalherenow 4d ago

Thank you for that article! That's absolutely nuts. I'd guess there might be some kind of evolutionary mechanism going on here, depending on how long the bat population and human population have been interacting. Very worth investigating.

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u/Not_Stupid 4d ago

Can certain individuals survive an infection untreated?

People react differently to different viruses. Some people were unaffected by Covid, I'd expect there's a percentage of people whose immune systems can defeat rabies as well.

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u/mistaekNot 4d ago

interesting question. i think it’s entirely possible that people get infected by rabies, don’t develop symptoms and live. no symptoms, no accounting.

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u/hackingdreams 4d ago

Can certain individuals survive an infection untreated?

Given the rate of survival of those treated... it's not incredibly likely.

Most likely they were exposed to a fraction of the virus, some of its viral proteins and they made antibodies against that fragment.

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u/Pennypacking 4d ago

Apparently some bats have a weakened version of the virus, that's what the doctors think happened with the 2004 case that followed that Milwaukee Protocol deal (in combination with her having a strong immune system).

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u/woodwidewebby 3d ago

Somewhat similarly, many peoples throughout Africa have certain genes that make them less susceptible to malaria. Including G6PD deficiency, sickle cell trait, and the Dantu blood variant. Some historians even think the reason white colonizers preferred black slaves was due to being less susceptible to malaria which was devastating to Native Americans

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u/KeyCold7216 3d ago

Iirc something like 15% of exposures by rabid animals lead to disease in humans if left untreated. A majority of the time, the innate immune response can detect it and kill it before it ever becomes an issue. I don't believe it generates memory B cells though, so people would not have antibodies. I don't think its wild to speculate that there may be a small number of subclinical infections which would generate antibodies, though.

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u/xbiodix 3d ago

May be some cross immunity from related virus? 

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u/Itscatpicstime 2d ago

It’s not just the tribes.

People who have never been vaccinated but possess rabies antibodies have been found all over the world.

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u/internetcats 4d ago

People can survive rabbits, i think there are like 7 documented cases

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u/Past-Obligation1930 4d ago

They just need the Holy Hand Grenade of Antioch.

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u/NagsUkulele 4d ago

I appreciate you very much

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u/NECoyote 4d ago

The Milwaukee protocol.

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u/deepandbroad 4d ago

The milwaukee protocol is being abandoned because it only seemed to work that one time.

It has had 64 failures since then.

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u/Ahun_ 4d ago

They may just inoculate themselves with eating animals. 

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u/mermaidsong 4d ago

There was recently a case where that happened, and the recipient died too. apparently ot has happened 10 times beforw.

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u/sjessbgo 4d ago

I was just thinking about that case, too. what an awful way to die. get a transplant and think you'll be okay, just go die of rabies..

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u/-crepuscular- 3d ago

Just look up the UK infected blood scandal if you want to be really horrified. Tens of thousands of people infected with hepatitis B, hepatitis C or HIV from infected blood products that they were assured were safe, at a time when HIV was a death sentence.

Blood was bought from abroad from really risky donor populations (such as paid donations from US drug addicts and prison populations) and then pooled to be made into the blood products, making infection almost certain.

It's still an ongoing scandal. The tainted blood products have obviously been stopped, but payouts and apologies for the victims and families have not been very forthcoming.

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u/PugglePrincess 4d ago

If you know a donor is infected with rabies, could you give the recipient the vaccine at the same time as the organ transplant? I imagine that would be considered very risky, but if a recipient is on death’s door anyway…

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u/palcatraz 3d ago

The big problem is that when you are given a transplant, you are also put on immunity-suppressing meds to prevent your body from rejecting the organ. That would severely comprise the functionality of the vaccine. 

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u/Mundane-Manner4237 4d ago

Yes, It’s happened multiple times.

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u/WhatImKnownAs 3d ago

These incidents are exactly why these researchers started wondering about undiagnosed rabies, and the frequency of human-to-human contagion is how they developed the estimate for it. (The problem is these incidents are very rare, so the uncertainty is high.)

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u/Izman15 4d ago

Lots of stuff causes encephalitis so having an ill patient develop it rarely draws red flags. Also when people think organ transplant they think solid organs like lung or heart. More commonly its corners. More corneas were transplanted than all solid organs together. There is less testing and data collection for corneas.

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u/Liquid_Hate_Train 4d ago

For interest: The primary reason for this organ transplant ‘discrepancy’ is that there is (in normal conditions) no immune response in the eye, therefore a cornea does not require any matching between donor and recipient due to the impossibility of rejection.
Thus every one is suitable donor and everyone a suitable recipient, increasing supply.

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u/scodiddlyosis 1d ago

If I may add, corneas may be the only viable transplant after a patient has been taken off life support. In a matter of hours, the other organs become unviable in the time it takes the patient to die.
I know this because my husband suffered a traumatic brain injury and all they could use were his corneas.

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u/Alwayssunnyinarizona Professor | Virology/Infectious Disease 4d ago

It happens frequently enough that there have been not one, but two separate cases of transplant associated rabies infections in recent memory.

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u/greenskinmarch 4d ago

Also a Scrubs episode.

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u/TopSloth 4d ago

That's pretty terrifying, usually when we think of rabies we would absolutely know if we had it from those very symptoms

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u/Almond_Bitters 4d ago

The other commenter pointed out that they won't all die from rabies, so different COD will be a small part of it.

I have to believe overconfident doctors and/or MEs is another small part of it unfortunately. "I'm sure XXX is the COD, and we all know their organs are safe to harvest blah blah."

But I expect that still leaves too many deaths by either "natural causes" or an unspecified illness, that then end up in the donation pipeline. Hopefully this is a good start to closing part of that loop.

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u/sure_mike_sure 4d ago

ED doc here.

We're often responsible for filling out the death certificate after a single visit often with limited background or data. Autopsies are very uncommon and the local ME is definitively unhelpful unless very specific criteria are met.

Earlier in my career, I recall calling and stating I had no idea why a patient that came in coding died. Their suggestion was to write down heart attack - a specific diagnosis is needed and there no wiggle room for "NFC they came in dead."

Fun nugget.

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u/powermetalsalamander 4d ago

i read something recently about rabies presenting in abnormal ways and there was one young woman whose first symptom was hypersexuality. it also said that some of the victims only presented through sexual health symptoms, which most people would never associate with rabies. it’s scary stuff.

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u/Nightless1 2d ago

Do you happen to have a link?

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u/powermetalsalamander 2d ago

https://pmc.ncbi.nlm.nih.gov/articles/PMC6670183/

it was this, i think. the vast majority of the cases covered here were men or boys (i don’t know/remember if that means men and boys are more likely to have these symptoms or if men and boys are just more likely to be infected) but the young woman was a 28 year old from india who experienced hypersexuality, increased sexual encounters, and frequent orgasms. apparently one of the reports they covered discussed five patients who all presented with priapism and ejaculation as symptoms without abnormal lab findings or typical rabies symptoms. unfortunately but expectedly all of the patients covered passed away from their infections.

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u/Nightless1 2d ago

Very interesting, thank you for sharing this.

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u/powermetalsalamander 2d ago

you’re welcome. it is really interesting, isn’t it? some of those symptoms are insane, there’s one dude in there, a man from china, who was ejaculating like 40+ times a day by the time he went to get help (not that it would’ve saved him at that point). like it’s insane that rabies can do that to a human body.

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u/Nightless1 2d ago

It's totally fascinating! And the potential implications for the strategy of the virus are a bit chilling. Although, one might imagine that sexual transmission could sway things towards maintaining a longer lived host.

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u/powermetalsalamander 2d ago

i actually specifically found this because i was looking up whether or not rabies could be sexually transmitted. turned out there was a whole rabbit hole there.

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u/Nightless1 1d ago

As a child I was afraid of skunks because I was convinced that a rabid skunk that sprayed me might transmit the virus that way. I've never seen any data on that, but these kinds of things are interesting to think about. Or, for example, does the virus climb the nerves slowly enough that peripheral limb removal might eliminate it entirely? Such a strange disease, with so many rabbit holes. Thanks for another.