Given that the symptomatic rabies leads to death in 100% of cases currently, wouldn’t it make sense to try a version of this in those few cases when someone in North America does get rabies?
They already tried the experimental Milwaukee protocol even though it wasn’t clinically established (and in fact didn’t work)
Once again, every single comment is picking apart the least important aspect of a comment. Though it works a small percentage of the time or not, the Milwaukee protocol is evidently not nearly effective enough, thus necessitating this research into a cure.
Your question stands: why not test it? There's precedent for testing unproven drugs on humans in extremis, so it's not that.
As a halfhearted stab in the direction of an answer: I assume they will try it in human rabies victims in a later phase, they're just testing it in mice first.
I might have been unclear: the Milwaukee protocol was not effective.
My point was, normal medical ethics seem to go out the window here. With most interventions, you can harm the patient, so you had best not give them anything until you test it.
But a symptomatic rabies patient is default dead. Given these results, it strikes me that we ought to move much faster through our usual phases and make it available for immediate use in centres which are symptomatic rabies patients.
If any of those patients start surviving, the drug has proven itself for general use and stats can be gathered. The control group is every prior symptomatic rabies patient: they all died.
The article made it sound like this will be something rolled out over several years. If that, as investment is required.
An estimated 59,000 people die of rabies each year globally. Each year of delay kills them. My question is should we not make this available immediately and see what happens?
It isn’t like heart disease where the patient will often live many years and so a new treatment must prove itself. Literally everyone dies of rabies if symptomatic.
Because there are so few late stage rabies victims that you simply can't get the data?
By and large in the US, people know the protocol--get bitten by a strange animal, head to the ER and get ready for rabies shots. And it almost always works.
Apparently, the US never had a post-treatment death until one 84-year-old man with an immune deficiency (and a bunch of other health issues) died of it. It's not clear anything would have worked for him.
https://www.unmc.edu/healthsecurity/transmission/2023/04/04/...
Basically, the only people who die of rabies are those who missed that they got bit or those who were dumb enough to refuse the vaccine. And there just aren't that many of them.
The fact that 20K people die to a disease that has a set of proven, relatively inexpensive treatments tells me that 20K people already can't get to a medical facility.
Getting to those people to a medical facility to test a new, unproven, expensive treatment simply isn't going to happen.
This is especially so since there are a vast number of diseases that are much higher priority than rabies in India.
I have unfortunately seen some heartbreaking videos where it's children who got it. Some for sure can't get access to medical care in the rural areas, but sometimes the kids might not even know.
I think there are some ethical issues with trying to find those people and not treat their disease before it is too late, most of the testing will consists of preventing people from becoming good test subjects.
I'm not saying it's bad, but it will be expensive and may fail to yield much result (as far as testing the cure goes).
Treating them is the point. Find people who's too late to get the old rabies shot and give the new treatment to them. The difficult part is control group but that's always the difficult part. Without control group they can probably just compare statistics with the past...
Post exposure vaccination alone is not sufficient to prevent death for all cases. Immunoglobulins (HRIG) must also be administered. HRIG is not commonly available in many developing countries or rural areas. This is why preexposure vaccination is recommended for vulnerable groups (children) when traveling to such areas.
That is not true anymore. There are two known protocols with a small chance of working but which have already saved about a few dozen lives. They are called "the Milwaukee protocol" and "the Recife protocol" after the cities they were developed.
Not sure about the Recife protocol, but it's pretty much accepted now that the Milwaukee protocol doesn't work[1][2] - the initial case may have been some other encephalitis mimicking rabies.
towards the end of the article, they say it makes sense to test in India because they get large numbers of advanced rabies cases whereas north america supposedly gets zero.
Rabies is such an unfortunate disease. It can live in you with no symptoms for months, and sometimes even years, and then one day you start presenting symptoms and the next day you’re dead. There’s no way to test for it because the way it’s tested for is by cutting your spine/brain apart…
I was exposed to a rabid bat a couple of weeks ago (captured, tested and confirmed to have rabies, unfortunately). While I’m not ecstatic about the cost of rabies treatment in America (it can be up to $40k a person, and 2 of us were exposed), I’m so glad we were able to get the bat tested and get in for the vaccines fairly easily.
The vaccines themselves are reasonably priced, but you have to get Human Immunoglobulin as well, which is only available at ERs and ranges from 2-12k per dose… and we needed 3 doses for each person (it’s by weight). In addition to those 3 shots, we had to get 4 vaccine shots, spread out over a 2 week period. Each shot caused symptoms. Luckily our symptoms were primarily just extreme fatigue or hot skin near the injection site, so it was not a fun 2 weeks but not the end of the world for us.
This alternative treatment sounds like it could be significantly cheaper and easier than that, and that it could possibly work in later stages, so that’s awesome to hear! I wasn’t clear from the article if they think it’ll be usable in humans once the symptoms begin though. If it’s before symptoms begin only, then it’s not much different than the current vaccine regimen other than cost/simplicity (which is still an awesome improvement, but not helpful for the people who don’t know they were exposed).
I've encountered bats twice at my house in semi-rural washington. One was hanging out in a can light on the ceiling of my deck... It meerly frightened the hell out of me, but didn't bite me; it made a kind of growl when I touched it, not realizing it was an animal. I came back some time later and it had left.
I found another one dead on the same deck a year or so later. As it wasn't white nose season, I had to dispose of it myself.
I’ve had rabies vaccines twice now; a bat flew into us out hiking and then a raccoon jumped me in our yard.
In no case neither myself or my kids had any discernible side effects. That’s interesting that was possible; considering the vagueness of early onset rabies (fever, fatigue, headache) that must have been worrying.
The worst about rabies is that it can linger for years; I heard of a case where a woman was traveling overseas and had exposure to a rabid monkey, and couldn’t get treatment for a week and then only got the vaccine, no HRIG. They told they won’t really know if it worked until 2 years, if she doesn’t die.
I strongly consider getting my family vaccinated before traveling to any place that doesn’t have ready HRIG and vax, since delay can be so dangerous. It’s a low likelihood but high consequences risk, but the vax is pretty low risk but expensive. Spouse doesn’t think it’s necessary so will have to cross that bridge.
No it would not be necessary. A control group would give you confidence that it wasn’t some other aspect of the experiment that resulted in people surviving. But we have strong enough priors on rabies that we should feel confident the probability of accidentally curing rabies with a different aspect of the experiment is extremely small.
If that were the case we could do a later experiment to establish that factor. “We’re doing ‘something’ that makes people survive” is good enough for a first attempt.
This seems like a trial that doesn't need a placebo group. We have a lot of data on people being infected with rabies and it's exceedingly rare for them to spontaneously recover. Basically, you could say the placebo trials have been carried out already.
No IRB would sign on to allowing a placebo group for a disease that has basically* 100% mortality after symptoms show, and the research group that tried would almost certainly be charged criminally for some murder charge or another.
*There's maybe a dozen known recoveries from symptomatic rabies, ever. So, 100%.
“ Low levels of the virus remained in the mice that received the antibody, but those levels didn't increase and signs of rabies did not immediately return, the results showed.”
I’m a little troubled by this outcome. Having the virus linger longer in a living host — is there chance it could mutate or exchange genetic material with another virus like an airborne one?
I don’t know how we would even measure when a human is truly cleared the virus; in mice they know because of an autopsy.
> Low levels of the virus remained in the mice that received the antibody, but those levels didn't increase and signs of rabies did not immediately return, the results showed.
Question: for the cost of a single treatment for symptomatic rabies, how many vaccinations could be administered? We might not be able to properly cure rabies, but we could possibly wipe it out. Even in animals, eatable rabies vaccinations might work.
Rabies lives in a LOT of animal populations (many asymptomatically).
Let's get a working cure for humans before we start worrying about sci-fi methods to eliminate a disease that's endemic in wild animals in many regions.
People do get vaccinated. Nearly every small town has a list of people (animal control, veterinarians) who are vaccinated in order that they can more safely deal with a potentially rabid animal. A dead rabid animal is still dangerous to handle. People who work around bats are also regularly vaccinated.
Cost and risk of the vaccinations vs risk of infection.
Many pets are likely to interact with wild animals that may carry rabies, but few humans are. Most humans with elevated risk of rabies are aware of it, and can get a sequence of preemptive vaccines.
Additionally, most humans bitten by an animal will consider rabies at that time, whereas few pets are able to provide a description of the animal that bit them.
All vaccines have possible side effects. I'd assume, not having researched the issue on this, but from general knowledge, that the possible side effects for a vaccine that would prevent almost no cases outweigh the possible benefits -- for the majority of people anyway. Obviously as the sibling comments explains there are some people who do need it.
They already tried the experimental Milwaukee protocol even though it wasn’t clinically established (and in fact didn’t work)