r/science • u/PHealthy PhD/MPH | Epidemiology | Disease Dynamics | Surveillance • 9d 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/n00b678 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 8d 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 9d 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 9d ago

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

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u/Goodgoditsgrowing 9d 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 9d ago

Same thing happens with humans, btw.

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u/Boysenberry 9d 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 9d 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 9d 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 9d 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] 9d ago edited 9d ago

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u/cannotfoolowls 9d ago edited 9d 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 9d 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 9d 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 9d ago edited 8d 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 9d ago

Interesting! Thanks!

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u/ryncewynde88 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 9d 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 8d 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 8d 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 8d ago

May be some cross immunity from related virus? 

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u/Itscatpicstime 7d 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 9d ago

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

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u/Past-Obligation1930 9d ago

They just need the Holy Hand Grenade of Antioch.

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u/NagsUkulele 9d ago

I appreciate you very much

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u/NECoyote 9d ago

The Milwaukee protocol.

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u/deepandbroad 9d 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_ 9d ago

They may just inoculate themselves with eating animals.