Eye doctor here:
some hot takes in this thread about the diagnostic abilities of the specialists involved in this patient's care. It's easy to be an armchair clinician.
The timeline for delayed immune reaction to a leptospirosis infection makes diagnosis incredibly difficult. There was no mention of an acute febrile illness preceding this during the patient's trip to the tropics, which I assume a uveitis specialist would ask.
While empiric treatment with doxycycline wouldn't be a bad idea, you have to decide what to empirically treat with, and for how long, and what the ramifications of increasing resistance to antibiotics are for society. Do I commit a patient to the hospital for two weeks of IV penicillin because I "suspect" syphilis? of course not.
Better diagnostics for these occult diseases should be applauded. But we shouldn't be vilifying the clinicians that are by all accounts doing their best.
I think there is a lot of hope because, in a purely research setting, this is extremely routine. The field of genomics is vast but the protocols are somewhat cheap and well understood. It's always hard to do a trial, and the tools are still often aimed at scientists (who are willing to spend months doing a single novel analysis), not point and click for a clinician. But even some relatively low hanging fruit will be extremely effective I think
A child is born with potential rare genetic disease. They sequence their DNA within 13 hours and come back with a diagonsis in some proportion of cases (they give lots of stats, it's small sample size, maybe 1/4 improved outcomes, maybe 2/3 have immediate change to their care)
> It was only after Ellie was offered a "last resort" analysis called metagenomics, that she was diagnosed with a rare bacterial infection which was cured with antibiotics.
After five years they'd never tried a broad-spectrum antibiotic treatment? That's the real story here.
The article literally says that all tests for infection came back negative. It is not said explicitly, but this heavily implies that she had negative cultures (not uncommon for leptospirosis) and did not present with things like elevated white counts (also not uncommon for this pathogen - especially for superficial infections). The article also clearly says they (mis-)diagnosed it as autoimmune disease and treated with steroids, which is pretty much the worst thing you can do in that case. Leptospirosis goes away most of the time without any treatment if you have a working immune system. So if you really need a contrarian takeaway from this editorial, it's that doctors are still sometimes more dangerous than diseases (which used to be true in general up until about 100 or so years ago).
"All tests for infection came back negative and it was assumed she had an autoimmune condition."
They never confirmed the autoimmune hypothesis but tried to treat it. What about the hypothesis of "it's some other infection our tests don't catch"? Antibiotics are a fairly simple thing to try. She got cataracts due to that mistake. Now that eye doesn't have dynamic focus.
Leptospirosis is very rare (~100 cases/year in the UK?) and typically affects other tissues (She's lucky it seems to have only infected one eye), making it more like a unicorn than a zebra diagnostically. Effective antibiotics are common, but even via IV they might reach not therapeutic levels in the eye.
Metagenomics are particularly good in cases like this where tissue samples are small. These spirochete are too small for light microscopy - probably why the lab missed them.
Given that leptospirosis is treated with doxycycline, you would have thought that they would have at least done a resistance study on the culture. Even if you don’t know it’s leptospirosis, you can know it’s susceptible to tetracyclines and treat it.
What I find most interesting about this story that antibiotics weren't given when the patient had persistent inflammation and a clear cause couldn't be identified. It seems like such a common low risk treatment just to try. Especially curious why auto immune was assumed instead.
Good question. I started having digestive issues a year and a half ago. Went to various doctors and according to their lab tests was told everything was fine, that maybe this was my "new normal." Recently had an infection that necessitated broad spectrum antibiotics and magically my digestion issues have cleared up...
If not for getting sick recently I'd probably still be dealing with whatever gut infection I had that the doctors essentially ignored.
Sorry for your situation, or I suppose, glad to hear it's better. My understanding as a layperson is that antibiotics can be a nightmare for the gut: I don't think it's particularly likely, but you are a lot more likely to get C. diff while taking antibiotics, and I'm sure that's not the only way it can make things worse, alongside the other caveats of antibiotics (e.g. people misusing them in ways that threatens their effectiveness.) So, I can understand why doctors are not always eager to deploy antibiotics when they're not convinced they will help.
I've personally had quite some experiences navigating health issues, health anxiety, the medical system, etc. Nothing terribly interesting, but, still. I'm actually in middle of scheduling tests to see if I might, in fact, have an autoimmune condition. If they do find evidence of that, then it will have taken me around 6 years to figure it out from my very first symptoms. Thanks to modern medical science, I have little reason to sweat over it, though. (Of course, I'm still hoping for a negative, but at least in the case of a positive I can have the relief of knowing what the hell was wrong with me all this time.)
Finding out I had gout was a 10 year process. Apparently "full test panels" don't include uric acid tests. And whenever symptoms are aggravated, it's much harder to test for it anyway as the crystals are lodged in your bones and not in your blood stream and urine.
Now I have to go through the entire process again to rule out everything else before getting a fibromyalgia diagnosis.
Anyway antibiotics have unrelatedly literally saved my life on several occasions now and I am glad that in a few emergencies I was able to access them on the street without needing to navigate the healthcare system. Antibiotics are too tightly controlled for humans and not enough for animals.
That said, I have had to take them enough that I've definitely experienced negative gut effects a couple of times. Now I reach for probiotics after a regimen.
I'm allergic to all cillins and had a spate of issues that required antibiotics 15 years ago, 3 treatments in 17 months.
I'll have to take probiotics the rest of my life. Because I'm not doing a fecal transplant, thanks. Those three times of antibiotics completely wrecked my intestines.
> Recently had an infection that necessitated broad spectrum antibiotics and magically my digestion issues have cleared up...
There are non-absorbable antibiotics designed to target intestinal bacterial overgrowth. It’s hit or miss, though.
Unfortunately for many people, taking antibiotics can have the opposite effect where it creates or worsens gut problems. It’s not an easy or reliable solution.
5-6 years ago my buddy and I got violently ill on a trip to Japan. Both agreed it's the sickest either of us have ever been, and we both lost 15-20lbs each. Shortly after our illnesses went away we both developed digestion issues. Went through stool samples and colonoscopies. He got diagnosed with uc and I got diagnosed with post-infectious ibs-d. Was told all tests were fine, but life since was hell. That is up until 2 months ago when I went to the ER with an infection.
Was given 2 weeks of doxycycline and voila, I'm no longer scared to fart, not running to the bathroom after eating anything, not going 7 times a day, and having solid stools. Might be tmi but whatever this is something that I'm happy and feel incredibly relieved (no pun intended) about.
Only problem is I still have what I went to the ER for, no one knows what it is, and I have to get another colonoscopy :/
Could you clarify what you mean by "dressed chicken"?
And I'm curious, did all of your family find yourselves allergic or sensitive to all of those things, or is that list a combination that covers everyone while each individual was allergic to one or a few of them?
One member did an allergy test and that found us major allergens. Rest of family just stopped eating those same things and things got better for everyone.
Dressed chicken, I meant to say broiler chicken. They are raised for the sole purpose of meat and the turnaround time is in 45 days or less now. They pump these birds full of lots of medication, vaccines and stuff. Everyone in the family gets sick eating them. OTOH, farm chicken that are naturally grown and have no medication is fine so its not chicken per se but maybe some medication or food given to these broiler chicken
I don’t know the details of this story, but I had an illness, and tried some antibiotics with no success. After a whole bunch more tests they decided it was a bacterial infection which had buried itself deep in my digestive system somewhere, and killing it required Fluoroquinolone —- which causes serious tendon damage in many people who take it.
It cleaned up my infection, and I didn’t have any side effects —- but hard to shift illnesses can require significant amounts of antibiotics with significant side effects.
We don't actually know that they didn't try first-line antibiotics. My guess is that they did, and it's one of the things that didn't work. The UK is a bit cautious about causing antibiotic resistance, but my understanding is that that's more of an issue with long term use so may not be the determining factor here.
Had this been in the US, good chance would have received doxycycline as first line treatment and the leptospirosis identified by metagenomic sequencing would have resolved
antibiotic resistance is such that it is increasingly less common to use it as just a "take 2 of these and call me in the morning" shot in the dark treatment.
It does feel like they don't hand them out as often as they used to.
I've had 4 infections this year, including an ear infection, fingernail, chest (that caused pneumonia on my son) and one that caused my left eye to swell up.
I received no antibiotics for any of them, just a suggestion that if they didn't go away they might prescribe some. They all got better without them (except my son, who ended up in emergency and was given two different ones which cleared up his infection rapidly).
In the past though I'm pretty sure I would have been prescribed them immediately.
It's an intentional policy shift that has come not only as guidance to medical professionals, but as an awareness campaign (posters in pharmacies etc.) to the general public that most minor infections don't need antibiotics, and so ones that the body should be able to deal with on its own will no longer be prescribed antibiotics.
It used to be that they were prescribed much more freely, because on the level of an individual case it's unlikely to do any harm and might help speed up getting better, and it was an easy way for doctors to make patients feel cared for to send them off with a prescription. But sensibly that's been course corrected now.
There's concern of resistance taken seriously for sure, but it's not like people are making out here - I had fluclox prescribed after an online consultation in Jan (for probable cellulitis) - they don't give it out like candy, but when it's indicated...
Maybe they tried something broad spectrum here, and what was necessary (and required the sequencing to know what it actually was) was something more targeted.
> In 2019, while still at medical school, Ellie began suffering from inflammation in her right eye. All tests for infection came back negative and it was assumed she had an autoimmune condition.
You know how everyone complains about antibiotic resistance? Yeah, they're not going to give some random antibiotic if they have no idea what something might be.
Antibiotic resistance is a problem for society. Infection is a problem for the individual.
Modern medical ethics requires you always prioritise the individual over society, which means one should always give antibiotics if the benefits outweigh the downsides for this specific patient, even if that means you might cause antibiotic resistance for everyone else in the future.
> Antibiotic resistance is a problem for society. Infection is a problem for the individual.
Unfortunately not necessarily. For many chronic conditions an individual may very well develop an antibiotic resistant bug. There's even plenty on YouTube about standard penicillins and strep bacteria that start growing right inside the antibiotics. Look it up, it's fascinating.
If you know they've got an infection then I agree that's a problem and medical ethics would suggest treating it with antibiotics if available. But, they didn't know she had an infection.
You're assuming (and indeed US medicine seems to assume this everywhere) that since there don't usually seem to be major negative side effects from antibiotics they're harmless. However we are now confident they're not - lots of interesting things live inside us and whether or not they can cope with antibiotics varies, we're an ecosystem and so this intervention is a massive change to that ecosystem, and while it will usually be justifiable if we know there's an infection if we don't know that's now a gamble.
What is a society if not a collection of individuals?
You don't get to complain about antibiotic resistance if at the first sign of an issue you demand a bathing in random antibiotics, especially if you don't even know if you have a bacterial infection in the first place
You can't claim to protect society from anything without protecting individuals primarily.
Society is not a herd in which you sacrifice an individual to save the rest.
The BBC article seems to overstate the uniqueness of the service at Great Ormond Street Hospital. While it’s true that they are the first in the UK to offer a UKAS-accredited clinical metagenomics service (UKAS being the United Kingdom Accreditation Service, which certifies labs to meet medical testing standards like ISO 15189), metagenomics itself is already being used in several other places across the UK.
For example, the Earlham Institute, the University of Oxford, and the UK Health Security Agency are all actively involved in metagenomics research and surveillance.
Regular doxycycline treatment is 5-7 days. She used 21 days of treatment. Meaning she may have tried antibiotics at some point, we are talking about 5+ years of history.
I'm currently struggling with my eyes. Over time my near vision started degrading as I'm approaching 50, then I hit that wall where it suddenly became a lot worse and I got glasses for the first time.
But the problem is that it generates a ton of eye strain for some reason, so now I'm on eye drops probably every 30 to 45 minutes and if I don't take them my eyes become really sore and useless.
At least I'm working for myself so its less of a hassle, but taking constant breaks to rest the eyes isn't great for productivity.
Have you tried "computer glasses"? (I.e., a glasses prescription that sets the focal length at around 60 cm (or whatever your normal distance to a monitor is).) It should help with eye strain as the ciliary muscle remains relaxed.
I would supplement vitamin A (10K IU), taurine (1g 2x/day), lutein (20 mg) (naturally derived), and zeaxanthin (4 mg). As for dry eyes, it is often triggered as an autoimmune condition in the absence of adequate vitamin D, but punctual cauterization can help.
> It is now presumed Ellie picked up the bug swimming in the Amazon river in 2018, while on a trip to Ecuador and Colombia.
Don't doctors always ask about international travel when you present with an unknown illness? The exact timeline is difficult to infer from the article but that seems like pretty important detail to overlook.
Doctors here in Europe are not really into diagnostic medicine. I'm going to compare with Dr. House from the TV series who with a team spent days on a single patient. This is not the reality, the reality is that your specialist doctor will spend 10 minutes thinking about your case before moving on to the next patient.
Keep in mind that even in the excellent documentary to which you refer, about Dr Hugh "House" Laurie, MD. PhD. McT., the premise is that his setup - a dedicated diagnostics team to focus on difficult to diagnose cases - is a rare concept, not something seen at most US hospitals. There wasn't, for example, a similar team in that other great documentary "Scrubs".
Primary care physicians do not spend more than two minutes diagnosing you in my experience. The diagnosis is always shallow and sometimes wrong because of how rushed the process is.
You pay a third of your salary in taxes, then you pay VAT on everything you buy plus many more taxes for other things such as your property. It amounts to more than half the money you earn.
> A value-added tax (VAT or goods and services tax (GST), general consumption tax (GCT)) is a consumption tax that is levied on the value added at each stage of a product's production and distribution. […] VAT is an indirect tax, because the consumer who ultimately bears the burden of the tax is not the entity that pays it.
(Even then, Wikipedia is oversimplifying: "ultimately bears the burden" isn't how economies work.)
"Metagenomics technology uses cutting-edge genomic sequencing, which can identify all bacteria, fungi or parasites present in a sample by comparing them against a database of millions of pathogens.
[if you] do a separate test for each and every one and if you've got an infection with something that's unexpected, rare or not previously known, you won't find it."
I'm curious if they initially diagnosed her with uveitis and began treatment based on that. However, I'm surprised there was no mention of consulting an infectious disease specialist.
In Canada, when a complex issue like this arises, it's common to see several different specialists; the testing is typically very thorough, even including some forms of genetic testing. They do everything they can to get you off the steroids, knowing it will cause issues if taken long-term.