Episode Transcript
[00:00:02] Speaker A: Welcome to ingest. My name is Charlie Andrews, your host for this series of podcasts designed for primary care clinicians and brought to you by the Primary Care Society for Gastroenterology.
In this episode of the podcast, I have a very special guest with me today, Professor Barry Marshall, to talk about Helicobacter pylori.
Helicobacter pylori is a bacterium that's found in the stomach and it is known to cause gastritis. It is one of the main causes of peptic ulcer disease alongside nonsteroidal anti inflammatories, and it's recognized by the WHO as a Class 1 carcinogen for gastric cancer.
Alongside Dr. Robin Warren, Professor Barry Marshall identified Helicobacter pylori and its role in gastritis in the early 1980s.
He then faced an uphill battle to persuade the medical community that Helicobacter pylori was a primary cause of gastritis and peptic ulcer disease.
But through hard work and persistence, these two men transformed our understanding of gastritis, peptic ulcer disease and gastric cancer.
Ever since their initial discovery of Helicobacter pylori in the early 1980s and its role in the development of gastritis, our ability to identify this bacterium, treat it and understand how it works has expanded enormously.
Professor Marshall won the Nobel Prize in Medicine and physiology in 2005 alongside Robin Warren for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.
He's managed a Helicobacter pylori research group ever since and is the Director of the Marshall center for Infectious Diseases. He's been awarded many honors globally for his work and is a member of many medical institutes and associations around the world. Professor Marshall is joining me today from the Marshall Centre in Australia.
Alongside work on infectious disease identification and surveillance, the Marshall center focuses on developing enhanced methods for studying and identifying H. Pylori.
During this episode, Professor Marshall is going to share his absolutely enormous knowledge of Helicobacter pylori with us. There'll be interesting anecdotes as we go through. He'll talk to us about the various tests involved and how we can maximize our treatment of patients with Helicobacter pylori. He'll also tell us about how he identified Helicobacter pylori and how he took the phrase taking your work home with you to the extreme when he carried out his first human trial with Helicobacter pylori.
So, Professor Marshall, thank you so much for joining me today. Why don't we start off by just talking a bit about what Helicobacter pylori actually is.
[00:02:58] Speaker B: Well, it's a bacteria, of course, as a microaerophilic, and these organisms like to live halfway between the blood oxygen and the anaerobic environment of the bowel, so they're more or less trapped in the mucous layer of the gut. Campylobacters, helicobacters and a lot of other gut, I guess, commensals and pathogens are either anaerobic or micro aerophilic. And so that's one of the reasons why Helicobacter doesn't invade the bloodstream. And people who are immunosuppressed, you know, they don't get septic from Helicobacter. It sits there on the stomach and really it's on the surface and it's really outside the body, if you like, and that it's on the surface. It's more like a dermatology condition of the lining of the stomach.
[00:03:46] Speaker A: That's a really helpful and clear explanation of what Helicobacter pylori is. I was wondering if you could tell us a little bit about how you discovered Helicobacter pylori and made the really groundbreaking leap towards understanding how Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer.
[00:04:11] Speaker B: So the thing about Helicobacter, nobody, although lots of people had seen it before Dr. Warren and I did our work, no one had connected up all the bits and pieces. And so we had the advantage of being able to take biopsies and cultures and study the physiology of the stomach and every. And then try and culture the bacteria, which we ultimately did. So we were pretty happy just to show that the medical texts were wrong to say that the stomach was sterile because at least 30% of Australians at that time, 50% of patients, and in developing countries, 80 or 90% of people in some places have these bacteria. And probably 100 years ago everyone had them.
It's only in the 20th century, there's been a bit of a gradual decline for various reasons.
So there was no doubt that bacteria lived in the stomach. And then when we were studying, you know, do they cause a disease? Well, Warren said, yep, they do. They cause gastritis, by the looks of it, because gastritis, everyone said that was caused by aging, some kind of inflammation in the stomach. It's just bad habits and maybe smoking, alcohol, all kinds of causes. Like in medicine, when we don't know what the cause is, you'll find a great big list of causes of all kinds of associations with things. So it was like that.
And one of the reasons people didn't believe helicobacter was important is because it was so common. It just seemed incredible that the disease caused by stress, which was duodenal ulcer, actually was nothing to do with stress. It's just a bacteria.
And the third thing was that there's no doubt that most people with the disease were asymptomatic.
So we had a 10 year uphill battle until we got pretty much past that and then got into the stage we're at now still in some places, which is, who do you treat, when do you treat it, how do you diagnose it? Should you treat everybody or just the bad cases and all that kind of situation?
And I'm happy that we are talking to general practitioners because one thing general practitioners love to do, they love to give people courses of antibiotics which cure them so that we can be very, you know, I guess, highbrow and academic about the helicobacter. But when it comes down to it, most people that find helicobacter are going to talk about it to the patient and the decision will be made to treat it.
End of story.
[00:06:57] Speaker A: Totally right. You know, when you find something that you can treat, it is very nice in primary care. And, you know, Helicobacter pylori is one of those. Just coming back to your story of discovery because it really is fascinating and that landscape of understanding was very different before you identified the link between H. Pylori and gastritis.
And was there quite a lot of pushback against your, your discovery and your, your theories that you proposed?
[00:07:28] Speaker B: Well, gastroenterologists didn't like it because, although, you know, maybe it's subconscious, but they had a vested interest in the status quo where they were making a living on endoscoping people with ulcers and then endoscoping them again a year later when they relapsed. So there was nothing in it for the gastroenterologists. And in fact, you needed to do a lot more with the patient if you're going to treat helicobacter. You had to make the diagnosis and then you would prescribe some antibiotics and you would do a follow up and you check again. It was quite complicated in the beginning, so I can see that people were slow moving. And the initial thing was, okay, let's treat the really bad cases when everything else has failed. So that wasn't too bad because a lot of people maybe they saved themselves from surgery. And Certainly by the mid-90s, gastric surgery for ulcers just about disappeared in Australia and a lot of other places. And surgeons weren't all that unhappy about it because they knew that although most people that had a partial gastrectomy for ulcers didn't do too badly, but there were 10% who were just terrible, no appetite, weight loss, dumping syndromes.
And there would be one of these people in every surgical clinic every week. So you could see it would get you down a bit, it'd make you in some ways keep away from gastric surgery if you could help it. So it was nice not to have to do it to people anymore. And it was also nice for curing H. Pylori ulcers. No problem, because by 1993, several double blind studies had shown that you almost got always got a total cure when you treated duodenal ulcers and eradicated H. Pylori.
And about 1989, 1990, some of the epidemiologists in the UK noticed the association between helicobacter and gastric cancer.
Globally, every country with a lot of helicobacter had a lot of stomach cancer and vice versa. Actually not 100%, but the hotspots for stomach cancer all had high background rates of helicobacter. And Warren and I had commented that as far as we could see, it was true. And everybody knew that nearly everyone with stomach cancer had gastritis.
And then when we studied our series of 100 patients and another hundred, etcetera, we couldn't find anybody with gastritis who did not have helicobacter. So it seemed like nearly all gastritis was helicobacter. And since stomach cancer patients had gastritis, well, it's quite likely that it was causing stomach cancer as well.
And so after some arguments, that idea was put out there and it was 10 years before people believed it.
Probably 84 was our first paper to the Lancet and by then there were people in the UK who were validating and say, yep, we're finding the same thing.
And the European top gastroenterologists and some in the United States, and certainly the infectious disease people around the world were on board with helicobacter as a potential breakthrough and, but it was hard to treat. So in those days you could give bismuth and amoxicillin and it was all very complicated.
But then when the PPIs came on the market, omeprazole in the 90s, up until about 95, 96, it was gradually moved into the system.
It was found that if you gave a, a good dose of omeprazole, you could use amoxicillin and another antibiotic or bismuth, you know, different combinations and get pretty high cure rates, up into 85, 90%.
And so at that point, okay, well, that was great.
And GPs and gastroenterologists were enthusiastic for a few years and they said, well, it's not very complicated anymore. We just hand it off to the gps. Once we've made the diagnosis, the endoscopy is done, we're losing money as soon as we see that patient again. So patients were then treated by the gps, and that's much better nowadays in Australia, I think medical students could go through our training course without ever seeing a patient with a duodenal ulcer.
If they've got helicobacter and they've got symptoms that could be an ulcer, will they get treated and that's it.
And Innis people sometimes ask me to collaborate on research related to stomach cancer. And I say, well, I've got some stomach cancer cases, frozen samples in the refrigerator.
I don't have any patients.
One patient in five years.
So that was great.
But you can see it's really moved a long way.
I'm thinking that when I was a medical student, I used to hear about tuberculosis and it was really hard to see a case, hard to find a case.
And it's a bit like that with ulcers now. I think people have got ulcers because they're taking non steroidals, maybe some other reasons, but so that nowadays ulcers would have about a, not more than a 50% chance of having helicobacter.
And you could probably diagnose a patient with helicobacter by just asking, taking the history, you know, where were you born? And did anybody in your family have it? Anyone have ulcers? And you could pretty much work out whether the patients probably just got gerd, which is now more common in western countries probably than Helicobacter pylori induced ulcers and things.
We've got helicobacter.
[00:13:46] Speaker A: It's amazing for me to hear how much we have progressed in our understanding of Helicobacter pylori since you first identified the pathogen in the stomach and in particular how it's had a huge impact on some of these conditions that previously were really common, such as peptic ulcer disease and gastric cancer. It's had a huge impact on the numbers of patients with those conditions. I wonder if now we could perhaps move on to how we diagnose Helicobacter pylori. Could you tell us about how you would do that in clinical practice?
[00:14:19] Speaker B: I use all tests, but I would screen with a serology. And in Australia, you can screen if you like, with a breath test. There's fewer false positives, so the government thinks it probably saves a bit of money and doesn't expose patients to unnecessary antibiotics.
The stool test is almost as good and doesn't need any preparation or anything.
[00:14:40] Speaker A: You've described three tests there. So we've got the serology blood test, the breath test and the stool antigen test. I'm certainly really familiar with the stool antigen test. That's something I use a lot in clinical practice as a gp, and I'm also familiar with the breath test. And I think that those are the two tests that we are. We often use in primary care or in the uk.
Not quite so familiar with the serology tests. And I think that our guidance generally advises us to use the stool antigen and breath tests initially. But I just wonder, would you be able to just talk through the pros and cons and just explain some of those tests a little bit more to us?
[00:15:24] Speaker B: Let's not worry about whether it's IGM or igg. I remember the professors used to give us crazy questions like that when I was a medical student. So, you know, you do a blood test and you look for antibodies if they're there, person's had the infection or they've still got it.
So depending on the history, you may go out and treat it just on the serology. But it's coming now to the stage now that fewer people have H Pylori and more people have a residual antibody. And so if you. I know that if you have a H pylori treatment, about 50% of people still come up positive on a serology test after one year.
So it's a good idea to repeat, to do a test which actually confirms presence of the bacteria. And so the breath test or the stool test, things that actually find organisms, serology says you've had it, breath test and stool test, you've got it. And it's not. None of the. No tests are 100% sensitive and specific. But I think one of the useful things of serology is you've got a patient comes in, you know, a white, you know, 30 year old woman with a bit of a stomach ache and she thinks she might have an ulcer or something. Well, you know, I put my money on that. She does not have an ulcer. She would have something else. Even GERD and I would do, I might sure put on a ppi, try this or that. But I might also do a serology and if the serology is negative it pretty much rules it out because serology is very sensitive.
So nearly everybody with, with H. Pylori or who's had it would have a positive serology.
If you've got a negative serology it means that you're a very unusual case.
I've seen people who just don't have antibody stage pylori or you've never had it.
So you would not put that at the top of your list if you had a negative serology. And if you say well you know, we're going to check your haemoglobin, liver function, whatever, analyze to the H. Pylori serology and so we can rule it out on the basis of that. But if it's positive you say, well, you know, there's a lot of antibiotic resistant ones around and I don't want to be treating you with all these antibiotics if I can help it.
So let's confirm it with a test that's, that's very specific. And so I always use a breath test at that point in, in Australia that's the number one test, the stool test.
Okay, that's fine. Stool test is great for children. But then we don't like to diagnose and treat children with antibiotics. It's too complicated. So wouldn't, wouldn't go looking for helicobacter very hard in children if you can help it, if you can find something else. So you go that breath test. Okay, the breath test is positive. Ah, so two things at that point if you, the thinking process is okay, you've definitely got helicobacter, no doubt about it.
Don't worry, we can eradicate it in two weeks with combination of antibiotics.
But where did you get it from?
So you probably caught it from your mother.
If you are from Latin America you could catch it in the drinking water. In Peru you could catch it in the drinking water. If you had been in Afghanistan or you know, any place where there's a lot of H. Pylori and you might be in the war or something, you could pick it up in the environment. But usually it means okay, who's the other person in your family who has it? So Every time you find a H. Pylori you say where's the rest of them?
And occasionally you find the whole family has it. And then you'll find that about a quarter of them are symptomatic and the others aren't.
So it's quite fun to chase down the H. Pylorism and you definitely treat the adults.
So the question is, let's say a 30 year old person who's got symptoms of an ulcer, there's still a good case to do an endoscopy. Is there reflux esophagitis as well? It's often hard to tell the difference.
And you might find people who don't have ulcers, they're just dyspeptic. And this is the functional dyspepsia, non ulcer dyspepsia patient.
And so those people, if you eradicate the H. Pylori and look after their symptoms for six months or so, 50% of them will be totally better. I remember Carmo Moraine did a study in Ireland and he published probably in gut, it might have been in Lancet, a study of treatment of non ulcer dyspepsia with a eradicating H. Pylori or just giving a ppi, following them up. And I think he followed them up for six months. And usually you have to do these things in a year so that the registrar could get his publication and move on to his next job so that they published it. But when he presented it and discussed it in conferences six months out or a year out, he was saying, look, I've seen these patients a year later and they are, a lot of them are really better who might have taken a bit longer to get better.
And the converse of that is I don't have a patient who said I was better before I had that helicobacter treated.
Please give it back to me. If patient wants to have it back, we can do that because we have it frozen in the refrigerator. But no one asks for it back. And if you look at the guidelines and say, well I'm. That's a bit conservative, I'm not really going to go with the guidelines. I'll have a discussion about it with the patient. And the patient says, so is it infectious?
Yes. Well, who can get it off me? Well, your partner, maybe your children.
And it's probably spread by kissing.
Okay, well that doesn't sound very good, does it? And is there a cancer risk?
Well, 60% of people have the CAG, a toxin on the helicobacter and they probably do a cancer risk, but it takes 50 years of gastritis, so don't worry, you won't get it till you're 70 or 80.
So, okay, cancer risk and you can spread it to the next generation. And there's a 10% chance that I'll be getting symptoms or an ulcer.
[00:22:17] Speaker A: I think if you said that to me, I'd be saying, yes, please, I'll take the treatment. Thanks very much.
So in the uk, in terms of who we treat, our guidelines suggest that we should try a treatment with a PPI first and then if that doesn't work, then test and treat for H Pylori. But I think in reality a lot of GPs will see a patient with dyspepsia and they'll generally do the test before starting because I know that there are certain things that can confound the results a little bit with the stool and breath tests. Is that right? Things like the PPI can alter the result and.
[00:22:52] Speaker B: Yeah. So once the patient's on a ppi, if they've got gerd, they might not want to stop it. You get a false negative result.
So you give the patient some omeprazole or whatever PPI you've got handy and see how you go. By the way, I go and have this, have a bit of a few blood tests and we do a H. Pylori serology and then 48 hours later the patient gets a phone call. It looks like your helicobacter is positive. So just stop that PPI for a few days and go and have this breath test.
If it's positive, I'll give you a course of antibiotics or. I know some gps are a bit slack and I know, I can think of a couple that I said, ah, I just treat it anyway before. I don't bother with those tests. So I don't, I don't agree with that because the compliance of the patient and the doctor is going to be much better. You'll get cure rates that are higher and you won't be partially treating H. Pylori infection creating resistant organisms, superbugs around the place. So be.
So be, I guess a bit disciplined and try a bit harder to get the follow up on the patients. And.
[00:24:12] Speaker A: In terms of people with acid reflux predominant, is that, is that, is that an indication? Is that a reason to test for H. Pylori or do people with H. Pylori not generally get primarily acid reflux?
[00:24:24] Speaker B: So you try to be a bit clever. If you take a history of the patient says, yeah, I'm getting acid reflux and take an antacid, feels better.
And.
And then you say, well, do you ever, ever feel, you know, like, bloated or nauseated? Do you ever vomit? If you start to get these other symptoms, they're a bit more gastric and they would really encourage you. Encourage me to, to try very hard to check the stomach.
So that'd be H. Pylori. But I. I would do H. Pylori test on everybody because some people with H. Pylori will have high acid secretion. So my anecdotal experience is that some people, when you treat their H. Pylori, they will get acid reflux symptoms.
Other people with apparent acid reflux symptoms will be much better when you treat the H. Pylori. Moiardi did a big study in Bristol and what they saw was that some people, they developed gerd, some people, the GERD went away. And that's why, on average, over a few hundred people, there's no signal of increased or decreased gerd. They say the H. Pylori makes no difference to those kinds of symptoms. You treat them separately or independently. So it's really just common sense, isn't it?
[00:25:47] Speaker A: Yeah, no, of course.
And just thinking now about treatment, if that's okay. So can we talk a bit about the treatment, treatments that there are? So in the uk, we start with triple therapy. Could you talk a bit about the basis for triple therapy and how you kind of approach a patient or would recommend approaching a patient with a positive H. Pylori, perhaps on breath test or stool antigen?
[00:26:12] Speaker B: If a patient takes lots of different antibiotics for things, UTIs, chest sinus, and they still have H. Pylori, you know that it's going to be resistant to a number of antibiotics.
So the way I classify these. Well, let me. Before we start, we'll say the number one breakthrough with H. Pylori was acid blockade.
And it's common sense that antibiotics that we use commonly are designed, in the pharmacology of the antibiotics, designed to go into urine to be concentrated in the urine, that is say amoxicillin, sulfurs or something, or concentrated in the sputum. Again, amoxicillin and even clarithromycin, roxithromycin, all those macrolides, they are good for the ent, the sinuses, ear infections, throats, that they're not designed to give high levels of active antibiotic in the stomach where there's acid. It's a different, totally different environment.
So it's not surprising that they don't work so well. So number one, remove the stomach acid.
And you notice the original treatment with for H. Pylori, it was called probably lowsec HP7, something like that.
That was 20 milligrams of omeprazole twice a day plus amoxicillin and clarithromycin.
Now we're using Nexium 20 milligrams twice a day. So that's really 40 milligrams of omeprazole twice a day.
So that's great. That's the starting point. Lots of ppi.
So don't be stingy with the ppi.
The second thing is the antibiotics.
There a group of antibiotics that H. Pylori cannot become resistant to. So that's good news. And so the number one of course is amoxicillin. So although H. Pylori might fail different treatments with amoxicillin in vitro and in vivo, probably they are still sensitive to amoxicillin. So you can always use that. The second one that you'll see around is bismuth and that's bismuth citrate. It used to be called, it's Dnol tablets, probably in the uk. But H. Pylori doesn't appear to become resistant to bismuth. The third one is tetracycline and you have an issue. You don't give it to children under the age of 16 or 17, you don't give it to pregnant women.
And in Australia you tell people, keep out of the sun because it makes you photosensitive or something.
Okay, so those three antibiotics, and there are a few others that I use because I run a special clinic for resistant cases and they're a bit toxic like furazolidone and erythributin. They're more or less TV type drugs.
But anyway, you've got those three, you've got, you've got amoxicillin, bismuth and tetracycline. So you can always add that into a treatment.
And then you've got the ones that are really strong, cytal, but H. Pylori will develop resistance to them.
And that is metronidazole, clarithromycin or any macrolide, norfloxacin, levofloxacin, any quinolone. You can imagine combining them in the right way, the ppi, one of those three antibiotics that always works and then one of the other three antibiotics on top.
And so that you can see, you can give easily give the Nexium HP7 and that's with clarithromycin. Amoxicillin, that fails. Okay, the second time around, we could still give the amoxicillin again instead of the clarithromycin, we could give a quinolone. And with two treatments like that from a general practitioner, you can see we're getting up to 90% cure.
And then it becomes a bit intellectual. You're looking at a patient who has got significant symptoms. They really seem to be related to H. Pylori. They go into partial remission and get better. They've got a resistant organism. So at that point you can get a bit fancy and the gastroenterologist can take biopsies, do sensitivities, infectious disease docs, or maybe you're a, a GP that loves H. Pylori. You can do fancy things. And in Australia, we've been doing it in China, is sort of getting involved with this is do a string test.
So the patient swallows a string inside a capsule and after an hour you pull the string out and on the end of the string you've certainly got some H. Pylori stuck there and you try to culture them. So if you can culture them, that's the best. That'd be 70% of cases. But at least you could sequence them with a PCR and look for the antibiotic resistance genes and get a sensitivity reading from that.
And we think that there's a lot of value in the DNA on the end of that piece of string. You know, is there a cancer down there? Are you at risk of this or that?
[00:31:14] Speaker A: I think in the uk generally, once we've tried second line treatment, we're recommended to refer on. And I think that's exactly in line with what you were saying about at that point. Point you're probably dealing with something quite resistant. And in terms of the testing. So if we are retesting, when should we do it? And does it matter what test we.
[00:31:33] Speaker B: Use when you're retesting? I'd say avoid the serology because the patient will get all excited if it's positive and most of them will be positive. So you just.
It's a big time waste to explaining the vagaries of serology results after you failed treatment or successful treatment.
Don't worry about the serology, go on to a test which measures the antigen, it measures the organism, counts it. At this point, it's just a thought I had a while ago that occasionally people, some people think, oh, yeah, well, we try to get the H. Pylori down to a safe level and it's so common, it's still There, but it's only 1% level and so don't worry about it anymore. That is not true. When you have a treatment for H. Pylori, it is gone. The whole, your whole body is sterilized of H. Pylori and you will not, you should not get any positive tests anymore. And so just avoid that. That's a fallacy about it being partially eradicated.
So then you're going to give your treatment and how do you manage this business? Of, of course, half the patients you see are on omeprazole, aren't they? Or ppi. I know this issue.
If you.
There was some nice breath test data where they suppressed H. Pylori completely with bismuth and then they did a breath test every day to see how long it took to come back. Well, it usually came back with three within three or four days. So realistically, if you stop the PPI and say it has a 48 hour action, then five to seven days after that you should be able to get a positive breath test, a positive biopsy, everything positive.
But you might have the occasional case that gives you a false negative and that's an issue. You don't want false negatives.
So Most people say two weeks off the PPIs.
Just make it two weeks.
Keep it as long as that if you can. And then you're absolutely certain if H. Polari is there, it will be growing back.
And my experience is that it doesn't go down to zero and then come back up to 20%, it comes up back up to 100%.
So anyway, you do the follow up tests two weeks after the PPI. So then of course then you've got 10% of your PPI patients.
I can't possibly stop taking this PPI, doc. I just reflux all night, it's burning me.
So that's a terrible situation. So what you could do is ask the patient to take an H2 blocker and antacid, see if you can get by on that.
[00:34:32] Speaker A: So those are okay?
Those ones are okay with testing?
[00:34:38] Speaker B: Not perfect. But you know, if I would say take ranitidine and take two or three or four tablets a day to try and control your symptoms and take Andes, it'll be getting a breakthrough. And then don't take anything and you'll just have to suffer for 24 hours before the endoscopy or the breath test.
And if it's rather a difficult case, the breath test is coming back borderline and the stool antigen is very iffy.
Go to a gastroenterologist and get Some biopsies. Occasionally you'll get patients who have reinfection from their partner.
So don't be frightened of testing the partner. Usually they're quite agreeable to get tested and they may be totally asymptomatic and they have got H Pylori.
So that in those cases I might treat husband and wife together. We have actually had a patient, she was in a study and we were doing this thing where we wanted to see if people could get reinfected with their own strain. So we were sort of asking this, you know, leading onto this thing, how easy is it to catch it again and again?
And so we had some patients, but one woman, we treated her and then she said, oh, the GP tested my husband and he's positive as well.
And so we treated him, the GP treated him and then she was negative and then she came positive again.
And the H Pylori appeared to be, because they weren't being treated in sync, that you would treat this one and it had jumped as if it was jumping away and going into the partner and then that one we treated, it would jump back into the. The patient again. So it became very confusing in that paper when we were looking at all the genomics, trying to figure out where this H Pylori really came from can be interesting.
[00:36:35] Speaker A: Wow, that's really interesting. And one of the things that I hadn't really considered myself was that if you have someone with H. Pylori, it's quite possible that someone who lives with them may well also have it. So that's definitely a bit of a take home for me. And talking about family and other people within that family unit. What about testing and treating in children?
[00:36:59] Speaker B: The issue with children, it's hard to do double blind studies in children because, you know, someone says, not ethical to give these kids all this invasive endoscopy, et cetera and biopsies and you've got to give them antibiotics and who knows what sort of symptoms they've got. So if you can get away with it, you don't want to diagnose H Pylori and have to give antibiotics to children if they're not sick, so don't test for it.
And this is the.
One of the rules in medicine, you only do a test if the result is going to change your management, otherwise you shouldn't do it. You just create problems for yourself and the patient. So people say, oh, little Johnny, actually I do clinics in China and this is a situation. So a woman comes in and she's got a 12 year old son she says, look, he's got a H. Pylori there, and I want you to treat it. And I said, well, how did you find out?
Does he have any symptoms? She says, no.
And I. So I was treating. Maybe I was treating her or her husband or somebody.
And I said, well, why.
Why did you check for it? Why did he have the test?
Oh, well, we just don't like the idea of our kids having H. Pylori.
So I was like, well, am I going to give. I can't give him tetracycline. I don't want to give him nfloxacin because he's in some kind of junior basketball league and he'll break his achilles tendon in five minutes.
So please bring him back when he's 16 or if he gets really sick or something. I'll, you know, we'll work on it anyway. It's caused all sorts of problem. You know, she brought him back when he was 13 and when he was 14, eventually. All right, all right, we'll treat it. We can't take it anymore. But on the other hand, you know, some doctors just don't believe that any. That some people believe that all stomach pains in children are functional.
I say, oh, well, he usually gets it on Monday morning. It's obviously school phobia. But I can tell you, even as an adult, I definitely feel worse on Mondays, and I'll take Monday off.
So kids are the same. But if you see a child is, you know, complaining about stomach aches, occasionally they vomit. They got a bad appetite. They may have. Even have funny things like chronic halitosis. And they may complain more or get sick on Mondays.
Check for H. Pylori, because that illness, if it's H. Pylori, could be totally cured. And it could be interfering with that kid's whole life at this stage by affecting his school.
And I've always got an anecdotal report, but when I was a registrar, nobody believed H. Pylori. And I said, that's Marshall's crazy theory.
I was a medical registrar and a child. She must have been about 14.
She Somehow we got consulted. She got into the adult hospital, and she got consulted about possible anorexia nervosa. And the family had caught her vomiting. So they're saying she's bulimic. And so I went sore. I couldn't find anything wrong with her. And when I asked her, took the history, she said, when I eat something, I just feel so terrible. The only way I can feel better is to go and vomit. And then I'm all right, but, you know, I just feel terrible about it.
So I snuck off a blood sample and did a serology on her, which we use, no commercial tests or anything these days, and she's strongly positive.
So I said to the family, well, you know, why don't we give her a course of amoxicillin and maybe we're using bismuth or tetracycline or something like that for a couple of weeks, see how she goes.
Anyway, so in that two weeks, she went to an outpatient clinic as well and saw a psychiatrist.
And so by 14 days, she was totally cured after being unwell for months and years.
And I'm sure everybody was saying, wow, that psychiatrist really must have done a great job.
You can see stories like that.
A gastroenterologist who believed all this conservative teaching, especially in the United States, are even more conservative than the uk, I think.
And he was African American guy, very good gastroenterologist, but, you know, he's following the party line. Maybe he was a pediatrician and his daughter had chronic abdominal pain and he, I think, somehow found out that she had H. Pylori. But the teaching was, you know, it doesn't cause dyspepsia in kids. His double blind study.
So for about a year he didn't treat her and she was sick every week and she was going down and down, eventually, you know, tearing his hair out. Eventually he gave her some antibiotics and she was better almost like overnight.
And, you know, he was carrying this burden of guilt that any less genius gastroenterologist, gp, any normal doctor around the town would have treated her as soon as she walked in the door for helicobacter, even though it wasn't mainstream.
And yet, because he was such a great specialist, he had to practice what he preached, and his daughter suffered as a result of that.
So I'm sure she's all right. Now.
[00:42:51] Speaker A: We're coming to the end. There is this story that you infected yourself with H. Pylori as well. What was your thought process around doing that? Were you worried about doing it?
[00:43:00] Speaker B: Did you feel, I'm not going to get a job as a clinical trials epidemiologist? Because I've published a paper with an n of 1.
I've actually published a paper with the n of 2 as well. Working up.
So the story was that to fulfill Koch's postulates, you want to try and infect an animal and see if the animal is going to get an ulcer. So that was way back in the early days. So this was would have been 1984. Warren and I had been working on it for three years at that stage and we're pretty excited, but we didn't have an animal model and we tried rats and guinea pigs and rabbits. And I can tell you, most of these animals, you can inject live H. Pylori intravenously and the animals don't even get a fever. It's just not pathogenic and it'll just get soaked up in the spleen, I suppose.
So I did run an experiment trying to infect piglets and we were endoscoping piglets and then we would take some biopsies and we feed them H. Pylori every night for a couple of weeks and then we would endoscope them again.
Nothing. So after six months, it was impossible to manage these piglets. So they were about 100 pounds and they were about six foot long. You know, they were turning into monstrous pigs.
So I got canceled that experiment and we might have, might have written it up, but I then decided to do human experiment and Dr. Warren, he had H. Pylori and I had treated him. So he had antibodies and it wasn't sensible to try and give him H. Pylori, probably would fail because he had antibodies.
And so I took a H. Pylori, a couple of petri dishes and drank them and I took a few tablets of cimetidine just so it wasn't too acidic.
And I was fasting. So I think I took them on a Tuesday morning and was 10 to the ninth organisms and I felt a bit dyspeptic, a little bit gurgly in the stomach for a few three or four days and then I started vomiting and. And that weekend both my wife and my mother commented that I had a bad breath.
And the beautiful.
[00:45:10] Speaker A: Very fast, it sounds like.
[00:45:13] Speaker B: So day five to day seven, you have the acute illness where you vomit.
And there was. I didn't notice, I didn't click at the time, but the vomit had no acid in it.
So in the acute H. Pylori infection, instead of getting an ulcer and bleeding to death or something terrible happening to you when you haven't got any immunity to it, the cytokines in the stomach turn off acid secretion. So H. Pylori's got this thing, it needs to get a foothold in there. It doesn't want you vomiting and dying. That would kill the whole plan.
We want to cause a chronic infection. We'll get rid of the acid, we'll get down right into the glands and the antrum and Hang out there and create a smoldering kind of illness there that lasts the rest of your life. So that's the perfect pathogen, if you like. Most people don't die, but they spread it to the next generation and everybody else. So that brings up some other questions. So is it useful?
So the thing about the H. Pylori is that.
So I was thinking about all this and writing this up and my father in law, my wife's father, had retired and gone on this great road trip around Europe and England. He was staying in Oxford and he used to go to the old bookshop. So he brought back William osler. Osler and McCrae, 1910 Textbook of Medicine.
They had a great big chapter on gastritis 1910, which I started reading. And it says, oh, in acute gastritis, a patient vomits for a few days and if you test the vomit, there's no acid in it.
So in those days the kids would be vomiting. They probably all catch it.
Kids would be vomiting, the mum would save the vomit and would do a house visit. And you dip litmus paper in the vomit. He's like, green. There's no acid in the vomit. Oh, don't worry. This is acute gastritis, achlorhydric gastritis. It's well known in the medical book.
And just give the kids some lemonade, flat lemonade and some milk, arrowroot biscuits and milky bread or whatever it was, and he'll get better in a few days. And. And sure enough, that used to be the situation. But of course everybody grew up having lifelong H. Pylori after that.
And as it became less common, it was taken out of the textbooks in 1966.
So Cecil's Textbook of Medicine dropped it in 1966. Everyone said, well, that seems pretty rare, we don't see much of that these days.
And that was better standard of living, smaller families, hygiene and normal things like that really combat H. Pylori. And the reason it's disappearing in England, not because everyone's getting antibiotics, it's just as the generations go, go along. Every 20 years it dropped by 50%.
So if it was 30% in year 2000, now it's 15%.
And in Japan, hardly anybody has it if they're younger than the age of 10.
And it's hard to do research on it anymore, you can't find those cases, especially in children.
But luckily everybody's got lots of Ukrainian refugees and Bosnian refugees, African refugees. Everybody's got displaced people turning up. And in Australia, they.
Those people have at least 50% infection rate.
And so that's where the. So in Australia, in my clinic, half of the people I would see be Vietnamese. Their parents were refugees. And then Middle East, Latin America, you know. So internationally people are moving around, migrating here and there more. And I bet you that's the same in, in the uk. Where are you? Are you in London?
[00:49:12] Speaker A: So I'm actually in Bath.
[00:49:13] Speaker B: That's famous place, isn't it? Did Charles Darwin used to go to Bath and have the cold water treatment or something?
[00:49:19] Speaker A: I'm sure every, every must have done that at some point.
[00:49:22] Speaker B: Is that near, that's quite close to Worcester and Gloucester, isn't it?
[00:49:26] Speaker A: Yeah, so not too far from Gloucester. I mean, you know, we're not far from Bristol. Bristol's our main city.
[00:49:31] Speaker B: Okay, I remember Bristol. That was, I went there. Or the Great Eastern, the first screw powered iron ship used to take people to Australia.
[00:49:40] Speaker A: I know, it's an amazing ship, that one.
[00:49:43] Speaker B: Yeah, yeah, it was, I enjoyed Bristol. It was great. Lots of interesting things there.
[00:49:49] Speaker A: So, but you haven't finished the story about when you, when you were infected with, with H. Pylori or when you drank your Petri, Petri dish full of H. Pylori because did you, okay, did you, did you have treatments ready in advance? Did you know that you could treat it?
[00:50:04] Speaker B: Well, you know, I did it secretly and my boss said he's doing the endoscopy. He says, barry, I don't know why you asked me to do this endoscopy and take these biopsies and I don't want you to tell me.
So he kind of knew that this was an illegal unsanctioned experiment.
So that went on. And after 10 days I had an endoscopy, really at the peak of the illness. And my boss, Dr. Hislop, who was ex Mayo Clinic stock, so blue blood gastroenterology, he took the biopsies and they were just covered in H. Pylori. The mucosa was just like wet blotting. Paper was falling to bits. But I didn't have any dyspepsia, I had no acid. And so then I said, okay, well we've proven the infection. Let's now want to get lots of EMS and good histology samples and every, you know, everything you think of. And next Tuesday I'll have another endoscopy and we'll get the good data. Publish this fantastic paper is going to be great. But in.
And I went home and told my wife at that point that I was infected with H. Pylori. Isn't it great?
And she's, she's there, like, what?
You'll infect me. You'll infect the family.
That explains why you've got a bad breath the last few days. I can't take it anymore.
It's too much, that kind of thing. And actually, she had been in a car accident. It wasn't terrible, but she did have a whiplash. It wasn't her fault, by the way. Some lunatic hit her on the side of the side.
And she had the kids in the car, so they were all going to the emergency room, and she had a whiplash.
And so the family was in chaos. And in the middle of it, I turn up, hey, good news. I've got a H. Pylori infection. I'm vomiting every day.
So she said, you get on the. Start the antibiotics immediately. And I said, calm down, calm down, please. I'm going to have an endoscopy on Tuesday. I promise I'll take antibiotics as soon as I've had the endoscopy. I did the biopsies, blah, blah, blah. She says, right, if you haven't started antibiotics on Tuesday, you're moving out.
So look how much a single room rent cost.
So we're.
So that was the situation. And I did take.
Start taking metronidazole on that day. As soon as I had the endoscopy, I was still feeling a bit unwell. I took metronidazole, but biopsies were all negative.
And so it turns out that a third or a half of people that have the acute H. Pylori infection will spontaneously get rid of it. And it depends on the surface antigens in the H. Pylori in your blood group and various other things, whether or not the initial infection is a tight match with your mucosa, and if that's the case, lifelong. And so you might, if you, if you're married to somebody, say, you know, 20, 22, you got married and your partner had H. Pylori, you would be exposed occasionally to H. Pylori because they would occasionally reflux a few bacteria into the mouth and kissing or whatever. So you would be exposed to that infection. But when we looked at married couples, only 50% of the partners were infected. And you say, okay, well, some of them would have already had it with a different strain. But when you check them, 25% of the partners were infected with the identical strain.
And so you can catch it, but also you can catch it temporarily, we think, and just become immune to that strain.
And that's all very well, in western countries you can see it would gradually go away. But if you lived in Peru, you're drinking water out of the river and 10k up the stream, there's people with sewage going into that river and then 10k further up the mountain.
If you've ever been to Peru, there's plenty of streams and mountains there, I can tell you.
Everybody's got H. Pylori coming from somewhere else in the water. Unless you drink bottled water, have your own water supply. So that kind of explains the epidemiology. The other one is how do you catch it? Will you catch it off your mother?
And a Chinese professor at UWA called Jack Shu, he said he came from Shenzhen, he said that used to be a fishing village and the mums would always chew the fish, get the bones out of the fish and then put it in the mouth of the baby. So pre mastication of food from mother to child is how over the generations H. Pylori was always spread to kids, end of story, if you like. And so we don't do that anymore. And with a bit of hygiene, smaller families, hot water, all that, we're going to get rid of H. Pylori gradually.
Yeah, but anybody, certainly anyone with symptoms, check them for H. Pylori and treat it and then figure out the rest of it at your leisure.
[00:55:08] Speaker A: That's. That is a good final note to finish on, I think, and that's really, really helpful. So thank you so much for joining me today. That was really interesting, you know, a game changing discovery and, you know, absolutely fascinating. So thank you so much for joining me today.
[00:55:24] Speaker B: My pleasure. And to the GPS out there, don't be guilty about giving people antibiotics. You're probably saving a few lives, that's my opinion.
[00:55:33] Speaker A: Well, that's the end of today's podcast and I really hope that you've enjoyed listening to Professor Marshall talking about Helicobacter puli.
It's quite unusual to speak to someone who's had such an impact on our understanding of gastroenterology. And I've just really enjoyed and felt inspired by the discussion today, and I hope that you have as well.
We've got plenty more episodes for you, so please do join me for further episodes, which we are bringing out every two weeks.
So coming up soon, we have episodes on chronic diarrhea, how to manage that. We're looking at inflammatory bowel disease with two fantastic speakers, Chris Lamb and Kevin Barrett. So please stay tuned and join us in the coming.
