> When they invented antibiotics, people began predicting "the end of disease." Fast forward a few decades and we have the rise of scary antibiotic-resistant infections.

> Medical stuff doesn't work the way most people would like to imagine it does. This sounds like a terrible thing to conclude. I'm rather unsettled to see it lauded here on HN.

Indeed, this exact thing is headline news in the UK today from our Health Security Agency - don't take antibiotics unless you definitely have something treatable by them: https://www.bbc.co.uk/news/health-59310099

Parasites are notoriously hard to treat. They are harder to treat than bacterial infection.

Places with lots of parasitic infections need better infrastructure and general hygiene to prevent infection. They don't need all the locals actively breeding drug-resistant parasites. Parasites are enough of a nightmare without cavalierly passing out drugs for funsies.

The WHO's guideline for "preventive chemotherapy to control soil-transmitted helminth infections in at-risk population groups" https://apps.who.int/iris/handle/10665/258983 isn't about "passing out drugs for funsies". They recommend mass drug administration for at-risk groups because hundreds of millions of people are suffering from parasitic worm infections that can easily be treated with a single dose of a cheap anthelmintic drug, but diagnosing every single case beforehand would be much more expensive.

Of course improving hygiene to prevent infection is important (that's also stressed in the guideline), but that will take much longer, while mass drug administration has immediate benefits.

Fear of drug resistance isn't a good reason to withhold treatment from people who really need it. The WHO's much more sensible strategy is to encourage research into alternative drugs in case drug resistance becomes a significant concern.

I’m certainly no expert but isn’t the evolutionary timescale for parasites considerably longer than for bacteria? That would presumably lead to quite different consequences (though of course the evolutionary pressure, and thus the risk, is still there).

Veterinarian here, used to ivermectin as it should be used - as an anti parasitic.

I fully agree with this view above.

You mean you believe that a widespread administration of ivermectin would lead to development of ivermectin resistance in parasites?

That’s certainly already the case. Ivermectin has lost effectiveness against particularly insidious parasites such as Haemonchus Contortus (barber pole worm). We’ve resorted to other treatments such as Moxidectin, Levamisole, etc, all of which are more expensive and harder to dose safely and effectively.

I can totally understand how Ivermectin got its following— it’s an amazing general purpose medicine around the farm. I generally use it responsibly by verifying the presence of parasites before administering (which can be literally any animal on the farm with almost any parasite) … but then there are times such as when my daughter had a single pet chicken (among many healthy ones) that wasn’t looking so hot … Whereas previously I’d just dispatch the animal and be done with it, now I give a dose of Ivermectin and isolate for a few days before calling in the grim reaper. So far the success rate is something like 90% where now my 9 year old daughter administers it herself. While I acknowledge this isn’t the most responsible, I can imagine others have had similar experiences which explain some of the popularity of Ivermectin with rural folk.

What's the downside of giving Ivermectin to livestock that don't have parasites?

Ivermectin stops working.

Through what mechanism?

Natural selection.

How will natural selection act on parasites if there are no parasites in the animal?

The drug may end up in the manure, and the parasites may encounter it there at a marginally-lethal dose. When the parasite progresses further in its life cycle, its offspring may be resistant when they infect the next livestock animal.

Most parasites have a life-cycle that includes time spent outside the preferred host animal, including in zoonotic species that may not have symptomatic infections. They may acquire resistance in any stage, in any place they encountered the drug.

It obviously cannot. But the issue isn't giving it to animals without any parasites, it is in giving it to animals with parasites but that do not need the anti-parasitic in order to recover. Once you have determined that the animal is sick enough to need treatment and that the sickness is most likely caused by the parasites, then you can make the decision that the risk of furthering resistance is outweighed by the need to treat the animal. If you have determined that there is no chance the animal has parasites, then there's no risk of furthering resistance but also no need to give the treatment.

I think this largely right, but resistance generally does not just evolve in the animals "that do not need it to recover", as all parasites/bacteria are more likely die in that case, but in more extensive cases where some of the parasites/bacteria survive and there are more reproductive events that can introduce a resistant genetic variation. This is why some consider that people not completing the full course of antibiotics- only taking them until they feel better, may be a greater contributor.

In nature, both the antiparasitic and the parasite will have a tendency to end up in places that you don't necessarily want them to be for the purposes of motivated hypothetical reasoning.

aka the chicken will urinate out some amount of ivermectin, unprocessed by the chicken, and then some amount will make it elsewhere that will allow for natural selection to take place (eggs or wherever). Once is infinitesimal, but give every animal some ivermectin for funsies, and you've now bred ivermectin resistance.

There's an issue with collies and collie-derived dog breeds; used to be warnings (even mentioned in an episode of "House"). But. Most of the lines running around today are the ones that weren't sensitive and didn't die from ivermectin. So it's no longer such an issue.

Widespread administration does lead to the development of resistant parasites. That's not an hypothetical, that's what you see on any farm if you prolong the treatment for too long.

It's always recommended that you cycle through different anti-parasite treatments.

Why would I take human medical advice from you? Are you saying there are no human uses beyond an anti parasitic?

I guess in theory you could use the topical cream form as a moisturiser. Perhaps even use the tube as a doorstop in a pinch.

Wouldn't we risk force-evolving ivermectine resistant parasites with the same mechanism as antibiotic resistant bacteria?

The CDC estimates that _at least_ 30% of all anti-biotic prescriptions are inappropriately prescribed. I'd wager an over-prescription of Ivermectin (that by some unknown characteristic appears it would save massive numbers of lives) isn't likely to evolve parasites (which evolve much more slowly than bacteria to begin with) to be resistant in a dangerously meaningful way given what we see with bacteria resistance.

This is of course just a gut feeling and not a studied understanding.

>This is of course just a gut feeling

I see what you did there.

I'm curious whether a similar mechanism would apply to the COVID vaccines? Can someone with some expertise in the area help clarify if this is the case? Are we accidentally creating vaccine resistant COVID strains with mass vaccination similar to how mass ivermectin creates ivermectin resistant parasites?

>When they invented antibiotics, people began predicting "the end of disease." Fast forward a few decades and we have the rise of scary antibiotic-resistant infections.

I think this is an extremely jaded take, resulting from growing up in a post-antibiotics society. The risk factor for those "scary antibiotic-resistant infections" is still an order of magnitude less than the class of diseases antibiotics almost totally eliminated. In the 30 years following penicillin's discovery, deaths from bacterial infection dropped from accounting for over 22% of all deaths to just 6% [1] (MRSA deaths, by comparison, currently represent less than half a percent). "End of disease" may be hyperbole, but between antibiotics and vaccines, infectious diseases were almost totally knocked off the leading causes of death.

The only reason why we even have antibiotic resistant bacteria is because they keep getting prescribed, because they're so damn useful. "Medical stuff" does, in fact, work like that, to some extent.

[1] https://dash.harvard.edu/bitstream/handle/1/8889467/Gottfrie...

The major reason why we have antibiotic resistant bacteria is because we use literal tons of the stuff for meat production and too many countries have too lax controls for antibiotic use in humans, which means they are taken for things were they don't help, or are not necessary, and are taken in the wrong dosage and for the wrong duration.

Exactly, if we only used it when there was a chance of it being effective that would be that, but instead your average cow is a walking antibiotic laboratory.

Malaria seems to develop resistance pretty fast. Are farm animals getting those treatments in their feed?

You will notice that the word "malaria" does not appear in the article cited. It is, thus, non-responsive, and no better than noise.

Anti-malarial medications are not antibiotics. Malaria has never responded to any antibiotic, to my knowledge. Maybe you don't know what malaria is?

I simply misparsed "those treatments" in your comment, thinking that they referred to antibiotics, which this threat is about after all. I'm aware that Malaria is not a bacterial infection.

> infectious diseases were almost totally knocked off the leading causes of death.

Well, until 2020. Then we had another infectious disease. Which is why we're having this conversation.

You have a valid point.

But note that it's a much easier point to make from a region where parasitic worms don't exist.