A New Lyme Disease Test In Development May Help Improve Treatment

ROXANNE KHAMSI: This is Science Friday. I’m Roxanne Khamsi. If you’re a fan of the outdoors and particularly if you’ve ever lived in the Northeast, you’re likely familiar with Lyme disease. It’s an illness carried by poppy seed-sized ticks. And if you’re unlucky, it can lead to issues like arthritis or even nerve problems. The CDC estimates that around half a million people in the US are diagnosed and treated for Lyme disease each year, but this number is likely an over count because many patients receive treatment based on symptoms without a positive test result.

Making the matter of counting cases even more complicated, the tests for Lyme disease can only detect if you’ve ever had Lyme disease. They can’t tell you if you currently have an infection, if the treatment you received was successful, or if you’ve been re-infected. My next guest is working to solve some of these problems by developing a totally new diagnostic for Lyme disease. Dr. Pete Gwynne is a microbiologist at the Tufts Lyme Disease Initiative, which is based in Boston, Massachusetts, my hometown. Dr. Gwynne, welcome to Science Friday.

PETER GWYNNE: Hey. Thanks for having me on.

ROXANNE KHAMSI: So before we get into how you’RE researching a new kind of Lyme disease test, can you tell me a little bit first about how the current tests work?

PETER GWYNNE: Sure, so we can’t test for the bacteria that cause Lyme disease directly. So we have to test indirectly, which means looking for the body’s response to the infection. So the current tests are all based on the antibodies that your body produces when you get the Lyme disease infection, which is why we have these problems with people continuing to test positive, even after the infection has gone away because that’s what antibodies are for. They hang around in your blood for a long time.

ROXANNE KHAMSI: Yeah, thankfully so, but I mean, how long can somebody still test positive for Lyme disease after, let’s say, they probably cleared the infection? Is there a record out there?

PETER GWYNNE: We know that people continue to test positive up to 20 years. I think it’s probably the case that a lot of them go longer than that. It’s difficult to study because it’s hard to get someone to come back to the clinic 20 years after they’ve been treated.

ROXANNE KHAMSI: So they’ve cleared the infection. They’re keeping those antibodies in circulation just to be vigilant in case they encounter the pathogen again. That’s fascinating. But your test is similar in a way, I guess. It looks for antibodies, but it’s a different kind of antibody. Can you say more about that?

PETER GWYNNE: Yeah, so we’re still looking for antibodies. But what we’re looking for is antibodies that have a very good response during an active infection, but then ones that will go away again as soon as possible after the infection has been cleared. So we’re looking for antibodies that have a strong initial response, but then a short kind of half life in the blood if you like, so antibodies that will disappear quite quickly after treatment.

ROXANNE KHAMSI: And there’s a certain new name for these antibodies or a special name?

PETER GWYNNE: The ones we’re looking for are anti-phospholipids. They’re not new, but they’re not as well-studied as conventional antibodies, which are raised to proteins. So every vaccine or every diagnostic test tends to be based on antibodies to proteins like, say, the COVID spike protein, which is what’s in the COVID vaccines. We’re looking for antibodies that are targeting a different class of molecule.

ROXANNE KHAMSI: So instead of proteins, they’re like fats or something like that?

PETER GWYNNE: Yes, they’re fat. They’re fats that make up cell membranes, so bacterial cells and also human cells and every other type of cell.

ROXANNE KHAMSI: Well, that’s what’s so interesting. It seems like these are antibodies that are actually against some of our own tissues. They’re kind of self-antibodies?

PETER GWYNNE: So the antibodies are against things that occur in the human host. They also occur in the bacteria. And we think the bacteria are kind of stealing these fats from the host.

ROXANNE KHAMSI: Whoa. It’s the only time I’d ever want to be upset about somebody stealing my fat, but sure.

PETER GWYNNE: Sure. Yeah, so the bacteria are really weird. They don’t make a lot of their own nutrients because they’re always in a host. They’re always in either a tick or a mouse or a human or whatever. They’re so evolved over time to basically steal stuff instead of making it for themselves.

So they steal these lipids from the host. And then we think we don’t know this, but we think that because these facts are now being presented back to the host in the context of a bacterial infection, they’re driving antibody formation, even though they’re fats that belong to the host if you like.

ROXANNE KHAMSI: Right, and so I think those are called auto antibodies. Is that right? Auto for self, like they’re antibodies against our self that have this mimicry type of thing where they’re also against the Lyme disease bacterium.

PETER GWYNNE: Yeah, exactly, so the antibodies are just any antibody that’s raised against host antigen, rather than a foreign and invading antigen.

ROXANNE KHAMSI: So it’s so interesting. So you’ve got this test, but can you tell us a little bit more about how this diagnostic test actually detects Lyme disease?

PETER GWYNNE: Yeah, so, again, we’re still looking indirectly. So we’re looking for these antibodies, which a marker of infection. So we’ve looked in small groups of people, and we find that these antibodies come up during an active infection, kind of before someone’s been treated. And then as we follow patients after treatment, we see that the antibodies start to go down.

ROXANNE KHAMSI: For these auto antibodies, not the ones that hang around for 20 years.

PETER GWYNNE: Yeah, exactly. So what we see is the conventional test, the antibodies that are involved stay high, like we’ve said. But others come and go as the disease comes and goes.

ROXANNE KHAMSI: Wow, so cool. So would using this test be able to detect if antibiotics work to treat the bacterial infection that causes Lyme disease?

PETER GWYNNE: Yeah, hopefully. So obviously, there’s a big problem with Lyme disease, which is that a certain percentage of people, 10, 20, 30, depending on how you count, continue to have symptoms even after they’ve had antibiotic treatment. So what we’re hoping for is that we can use this test to help diagnose some of those people and to help manage those long-term symptoms that some people are getting.

ROXANNE KHAMSI: And there’s some weird history as well in terms of how syphilis has something going on that’s similar to this. Can you say something about that?

PETER GWYNNE: Yeah. So syphilis feels like a very different disease, so I understand. But syphilis is actually caused by a very similar bacteria to Lyme disease.

ROXANNE KHAMSI: Yeah, last I checked, you can’t get syphilis just taking a walk in the woods.

PETER GWYNNE: I guess it depends what you’re doing on the walk, but no, largely not. So the way they diagnose syphilis is they have two different tests. You have one test that’s very specific. So if you test positive for that, then you’ve definitely got syphilis. But that test has the same problem that the Lyme disease tests have where you stay positive for the rest of your life. So what they do for syphilis is they add on a second test, which is less specific.

So you couldn’t use it to make the initial diagnosis. And so exactly like we’re seeing, they see that this second, this sort of add-on test, declines over time when treatment’s been successful. And when treatment hasn’t been successful, those antibodies stay high. So we’re basically hoping that we can use our test in the same way. When the antibodies go down, the treatment looks like it’s worked. If the antibodies stay high, maybe the treatment hasn’t worked. And we need to look at either continuing treatment or trying a different treatment or whatever.

ROXANNE KHAMSI: And I know that antiphospholipid antibodies, these self antibodies against these fats in our cells, are kind of a little bit like an antibody du jour. And I know that people are looking at them for COVID. Is there a way to say if somebody tests positive for these auto antibodies that we’re sure it’s a Lyme disease signal and not something else?

PETER GWYNNE: That’s a really good point. And we’re still looking into that as far as our test is concerned. We’re still testing all the different possible diseases that might interfere with the test, that might get false positives. So we’re still trying to work out exactly what the specificity of our test is. I think one way of getting around that is, like I mentioned, you pair the test with a more specific test. So one test doesn’t have to do all of the things you need, right?

ROXANNE KHAMSI: And there are researchers looking at other kinds of tests for Lyme disease, right? New tests.

PETER GWYNNE: Yeah, definitely where Lyme disease is really a very active research community. There’s a lot of people looking at all kinds of different aspects of the disease. Yeah, there’s a lot of people looking at different kinds of tests, either trying to develop ways to detect the bacteria directly, which like I said, we can’t currently do, but maybe we can find a way. And also people, yeah, looking for other ways of detecting them indirectly like we’re doing. Yeah, hopefully, one of us gets it.

ROXANNE KHAMSI: So Lyme disease is caused by this nasty bacterium in ticks, Borrelia burgdorferi. Why can’t we just do a simple test that looks for that bacterium?

PETER GWYNNE: That would be great. And for most bacterial infections, the kind of gold standard for diagnosing them is, you take a sample and you drop it into some growth medium. And you see what grows. And actually, that doesn’t sound very scientific, but it is a pretty reliable way of diagnosing most infections. The problem with the Lyme disease bacteria is they grow quite slowly. So even when we do it in the lab under perfect conditions, they take about a week to grow. And no one wants to be waiting for a week before they can make a diagnosis.

The other problem is where you’re sampling from in the person. So again, if you’re diagnosing a skin infection, you can swab someone’s skin. That’s easy. Even if you’re diagnosing a bloodstream infection, you can just take a blood sample. Lyme disease doesn’t stay in the skin for all that long. And it doesn’t stay in the blood for all that long. The places it kind of swims to once it gets into your body are not easy places to sample.

ROXANNE KHAMSI: And where are those places?

PETER GWYNNE: Your joints, your spinal cord.

ROXANNE KHAMSI: Oh.

PETER GWYNNE: Based at the heart, none of which are easy places to just take a quick swab from.

ROXANNE KHAMSI: No, no.

PETER GWYNNE: You can sometimes detect from synovial fluid, the sort of liquid that’s in your big joints. So if someone gets treatment for arthritis, and they have some of that fluid drawn, then you can sometimes detect the bacteria in that fluid. But if someone goes into the doctor’s office and says, I’ve got a bit of a fever, and I was out hiking, you’re not going to jump straight away to sticking a needle through their knee.

ROXANNE KHAMSI: No, or a spinal tap, I would think.

PETER GWYNNE: No, that would be even worse.

ROXANNE KHAMSI: So a really big part of this Lyme disease conversation recently has been about people who have chronic symptoms. So would this type of antibody test that your lab has worked on and developed determine if somebody has a persistent infection?

PETER GWYNNE: We hope so. We’re not there yet. We still need to do a lot of work. We’re about to start that work, looking at a bunch of people with those kind of chronic symptoms, the persistent symptoms. But we think it might. The problem is at the moment, we basically don’t know what’s causing those as a field. Those symptoms could be caused by an infection that hasn’t responded to antibiotics. It could be caused by something going wrong with your immune system. You had an infection.

Everything has become out of sync. And then it’s just taking time to kind of go back to normal. You could just be really unlucky, and you had Lyme disease, and the Lyme disease went away, and now you’ve got another disease. That’s unlucky, but it happens. So we don’t really know what’s causing those symptoms yet. So we’re hoping that one of the ways this test might help is either for helping to diagnose those people or even just for screening people into clinical trials.

At the moment, we don’t really have any good idea what to do with those people who continue to have symptoms. To find out what the best treatment options are for those people, then we need to run clinical trials. At the moment, it’s hard to know who to include on those clinical trials.

ROXANNE KHAMSI: And I know a lot of people listening are curious to know when they might have access to this test. I know you have a provisional patent for this test you’ve developed. What kind of timeline are we talking about? What further research is needed before they can have access?

PETER GWYNNE: Yeah, so this is definitely still just a thing under research at the moment. The test doesn’t exist in a way that we could make it accessible to the public. I think it’s reasonable getting tests like this approved. Diagnostic test is a faster process than getting drugs onto the market. So that’s good news.

Bad news is it’s still not a super fast process. We still need to do more science in the lab. And even after we finished all the bench science, then we need to build a machine, an actual device that can run these tests in clinics or in hospitals or whatever. I think we could submit to the FDA within five years.

ROXANNE KHAMSI: Wow.

PETER GWYNNE: If we’re able to raise the funds to get that done.

ROXANNE KHAMSI: This is Science Friday from WNYC Studios. If you’re just joining us, we’re talking about a potential new diagnostic for Lyme disease and how our current tests are falling short.

At the same time, there’s work on a Lyme disease vaccine. I guess it’s the second iteration or a further iteration since there was one on the market for three years or so or two or three years, maybe 20 years ago. But there’s a new one on the horizon, and I was wondering, are you optimistic about it? Would it change some of the testing and treatment strategies for Lyme disease?

PETER GWYNNE: Yeah, I mean, hopefully, if the vaccine works, then it means you would need to run fewer diagnostic tests, which would be bad for business, but good for the world in general. So I’m happy to take that hit. I think what we’ve seen with this new vaccine is very promising. It’s actually quite similar to the old vaccine, which is good, I think, because the old vaccine actually worked reasonably well.

So hopefully that’s good news. And hopefully, I think the data from the initial trials has been really good. And they’re going into the third and the final stage of the vaccine trials process. So I think everyone’s kind of optimistic about that vaccine. I definitely think that reducing cases is going to need a whole load of different interventions.

So vaccines will help. Getting better tests for people who are suspected of having Lyme disease will help. Having better treatment options for people who have definitely got Lyme disease will help. So I think, yeah, it’s good to have people working on all of the different angles.

ROXANNE KHAMSI: So none of this sounds like a walk in the park, that’s for sure, but it does sound important. I’d like to thank my guest, Dr. Pete Gwynne, who is a microbiologist at the Tufts Lyme Disease Initiative based in Boston, Massachusetts.

PETER GWYNNE: Thanks for having me.

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