Q&A about Lyme disease and the DualDur test with András Páll Bózsik

Not all doctors report it, and not all doctors are even able to recognise it, so we only have estimates of how many new cases of Lyme disease there are each year in Hungary, said András Pál Bózsik, head of Lyme Diagnostics Kft., the company that developed the DualDur test, to Weborvos. We also asked him why Lyme disease is so difficult to diagnose.

It can be said that what we know about Lyme disease has completely changed over the past 10 years. If we look at the doctors currently practising, a quarter of them graduated when this disease was not yet known. The pathogen itself has been with us for thousands of years, it has been known for about 150 years, and in 1982 it was identified as the cause of the symptoms of Lyme disease. Since then, we have been talking about the existence of Lyme disease. My father, Dr. Béla Bózsik, participated in the description of the first cases in Hungary, and they published the first cases as early as 1985. Obviously, they had patients with similar symptoms before that. He worked at the central laboratory of the National Institute of Public Health, and his job was to develop tests for any new diseases and pathogens that were detected. And since testing for syphilis, which is a very similar pathogen, was part of his job, he was able to develop the tests that we still use today.

In Hungary, and indeed everywhere else in the world, it depends on how many people report this disease. Previously, the statistics showed the number of reported cases. In Hungary, doctors reported approximately 1,400-1,500 cases of Lyme disease between 2018 and 2022. This number is increasing; last year it was significantly higher, on average 37% higher than the previous median. The NNK regularly publishes these statistics. It is important to note that American and European estimates are ten times higher than the actual number of cases. Why? Because not all doctors report cases, and not all doctors are able to recognise them, so there is a factor of ten. This is why, based on the number of reported cases in the US, which was 30,000 about 15 years ago, they have reached the point where, based on the number of cases reported by the TB, they report 476,000 patients annually, which they say is the official estimate of how many patients there are. This means that in Hungary, there are currently 15,000 to 20,000 cases per year, and since a significantly smaller proportion of these are treated, the number continues to accumulate. My father already reported the actual number of cases in Hungary on The Lancet professional portal about 15 to 20 years ago.

What we later saw, published in one of the British Medical Journal’s publications, was a meta-analysis that definitively stated that globally, approximately 15% of people are affected by Lyme disease, and in Central Europe, this figure is 20.7%. This is the presence of a seroreaction, which means that we have already encountered the pathogen. So, for every fifth person, if they have symptoms similar to Lyme disease, it is worth considering that it may be caused by Lyme disease.

There are an increasing number of diseases for which Lyme disease is considered a possible cause, either as a primary or additional factor. To name just a few: multiple sclerosis, ALS, certain types of diabetes, autism, all of which may not have a single cause, but if Lyme disease is present and cured, the symptoms can be reduced or completely cured. So it can be said that in almost all diseases with similar symptoms, it is worth considering that Lyme disease may be behind the problems.

From the patients’ perspective, in more than half of the cases, they have to wait more than two years for Lyme disease to be diagnosed. These are older American data; there is no similar research in Hungary. These statistics were compiled by surveying thousands of people with Lyme disease to find out how many years it took to diagnose them, and for a large proportion of them, it took more than six years. If we look at visits to the doctor, which do not refer to commercial activities, but rather to actually going from doctor to doctor, 72% of patients saw more than four doctors. So the problem is enormous.

This is currently the most common animal-to-human disease carried by ticks, which is why we talk about it all the time. In all such cases, the doctor and the patient can solve this problem together. Not everyone has a doctor who thinks of this immediately.

I have spoken to about 300-400 doctors so far, either in person or at various conferences and international medical conferences. We have educated Hungarian doctors, both at universities and by organising various training courses, and the truth is, and this is one of the most important things, that there is a lack of information about when to think of Lyme disease. The other problem is that they do not consider that this disease is more common than one might think. They simply think of it as an autoimmune process and treat the patient with steroids instead of considering that the autoimmune process may have been triggered by an infection, and one of the most common infections that cause autoimmune processes is Lyme disease. We see a lot of different opinions, but I can say that doctors are generally open to this information, and more and more of them are sending patients to us to tell them what to do next.

The red spot, the Lyme spot, theoretically, if someone notices such a spot on themselves, it is probably Lyme disease. Why is it that doctors or potential patients still do not recognise Lyme disease?

The fact is that statistics are responsible for this. We have now tried to compile a list of cases where such a spot appears, a rosette-like spot, which is a skin inflammation spreading around the bite, a redness, to see if there are cases where there is such a spreading redness and yet we are not talking about Lyme disease. And the truth is, there aren’t many. So we can say that if this redness appears, then it’s definitely Lyme disease.

The problem is that in the past, this was included in the descriptions as a mandatory diagnostic element, so anyone without redness could not have Lyme disease. Thus, statistics showed that 98% of people with Lyme disease had redness. That’s because that was the condition. In reality, we conducted the largest clinical study in Central Europe and found that 45% of our patients had Lyme rash, and current publications put the average at 30-40% of those who actually develop it. And you have to notice this, you have to pay attention to whether this skin symptom has developed.

These symptoms creep up slowly, and you may not notice them until there is a sudden worsening or a sudden weakening of the body. You will only notice it when the symptoms worsen. The first symptom is some kind of itching at the site of the bite, possibly followed by redness. As with any other infection affecting the body, it develops into what is known as summer flu, with fever, slight weakness, muscle pain, headache, fatigue and lethargy. This is what should first make you suspect that something more is going on. And of course, we cannot yet say what the cause might be, because there are so many things that can cause such a sudden headache or slight fever.

It can be said that although this disease affects the entire body, the symptoms go in two directions. One is neurological. According to our measurements in Central Europe, the most common type of pathogen is Lyme disease, which causes neurological symptoms. These include headaches and forgetfulness, and can even progress to a condition that affects the entire body, such as multiple sclerosis, which can also be treated with antibiotics in such cases. So there can be various nervous system problems, pain, and musculoskeletal problems, most commonly joint pain. It does not necessarily swell up enormously, although we have recently seen cases where a small child’s knee swelled up enormously, but basically these are various joint pains, which, as in Hungary, where various rheumatic pains are usually treated in medicinal waters, can also be alleviated by warm baths. These are the two main types, and serious heart symptoms are very rare. This is a disease that affects the entire body.

Not everything is Lyme disease; there are numerous co-infections that weaken the immune system and open the door to various infections, which can then cause even more serious symptoms.

My father, as a serology expert, was the first in Hungary to test for Lyme disease using serological methods, which means measuring the immune response. But it quickly became apparent that this pathogen can weaken the immune response. When a tick bites, it prepares to suck the person’s blood for a long time, so it should not be attacked by the immune system. It is prepared for this and weakens the immune response. That’s where it starts. Then the pathogen itself can weaken the immune response, which is why in about a third of cases we see no immune response at all. And beyond that, it depends on how good the test is. In less than half of infected cases, we see a positive result on the serological test.

Imagine that there is a deer, we see its tracks in the mud or on the ground, and something is moving in the bushes. The question then is whether I should take my rifle and shoot at the bushes. We know of hunting accidents where shots were fired and it wasn’t a deer in the bushes. This means that the trace of the pathogen in the body is not enough for me to shoot the deer in the bush, i.e. to shoot it with antibiotics. There is simply not enough information. So it would be easier to measure the pathogen itself to see if it is present in the body or not.

Obviously, there are several ways to measure this, but this pathogen is very volatile and likes to be present in the blood in relatively small amounts. And because it is variable, it cannot be measured by all methods, only by methods that are not affected by this variation. My father realised that, as with syphilis more than a hundred years ago, the solution here would be the microscope, because the shape of the pathogen is a very good indicator. The way it moves clearly proves that it is a spirochete, which performs a specific movement. And we can say that if this pathogen moves like this under the microscope, then it is a spirochete in the blood. We were able to confirm what it causes and what type it is, that it is Borrelia, with a specific stain. We said that we would produce an antibody against Borrelia, which we would mark with a dye, and it would stick to Borrelia, specifically only to Borrelia. That was the basis, that was the idea from which we created the DualDur test.

This pathogen is present in relatively low concentrations in various body fluids, but my father realised that, compared to typical blood infections, about a hundredth of the pathogen is always present in the body. I won’t be able to detect this pathogen from a single drop of blood, but if I take, say, four millilitres of blood and concentrate the pathogen content to about a hundred times, then I have a chance of catching it. He sensed this at the beginning, forty years ago, and then, prior to our clinical research, we proved it technically that yes, the level of this pathogen is about one hundredth of that of another pathogen present in the blood, which causes very serious, high fever symptoms, but does not belong to this type of pathogen.

As long as the test was performed by highly qualified assistants and chief physicians in the laboratory of a national public health institute, it was very good because we could trust that their professionalism would rule out human error. Our primary task was to try to make this test available in such a way that it could be automated, eliminating inattention, the possibility of a sample being prepared incorrectly, or someone having a bad day and not noticing the pathogen under the microscope. That is why we use artificial intelligence with an image recognition algorithm that scans the entire sample for precisely these moving pathogens. And that’s when we realised that it’s not enough to find a few pathogens in the blood, because our method concentrates the pathogens so much that we would find even a single one. But that’s not enough; we need to calculate statistics on how many were present in the sample. Based on this, we can then categorise who is experiencing symptoms and who has the pathogen but is not experiencing any problems.

The doctor who sends the patient to us has an opinion as to whether the patient is healthy or sick. And to be as accurate as possible, this 96% means that we can find 96% of the suspected patients.

I would not say that doctors do not need indirect tests, as they do not show the fact of infection, but they do show the state of the immune system. We also offer a serological test, which my father has refined from the original. It also gives very good results in determining whether someone has an immune response or not.

However, the direct test tells us whether the patient is currently infected or not. We have a scale that shows the level of infection. Unfortunately, we have had to introduce a fifth level, which we now call high positive. We will be introducing it soon, and there is also a completely infection-free level. And between these there is a level, the so-called cut-off level, which separates the positive from the negative. So we tell the doctor how infected the patient is, and we also tell them whether the infection is likely to cause symptoms or not.

Yes. As I said about the symptoms, it is quite common for someone to have a latent infection, from which they feel very minimal symptoms and notice very little. To a Lyme specialist, this would be obvious. These symptoms creep up slowly, and then one day you realise, hang on, I wasn’t like this ten years ago. I can say this from my own experience, because when I experienced the first bout of stress that I couldn’t cope with, I completely broke down and had to be treated for Lyme disease before I could go back to work, because I felt that I had aged, even though I wasn’t even 40. I had aged because I couldn’t do the same things, I didn’t trust myself, and of course there was pain and forgetfulness, which we could have deduced from that. That’s when my father told me that I had actually tested positive back then, but I had gone abroad and they couldn’t treat me at the time. The symptoms appeared when my lifestyle changed, I started working in an office, and I was under a lot of stress.

Well, if you are very lucky and get to see a Lyme specialist who asks about your medical history and you experience symptoms, you can be diagnosed in two to three weeks.

Our test can detect the actual infection after just four to six days, but even then, the test may show only a slight positive result. So there are symptoms.

We do not determine the symptoms, but the characteristics of the pathogen. In the case of an early infection, it comes down to whether the person wants to be treated or not. In the case of a pregnant woman, where there is a higher risk of miscarriage if there is an infection, it is generally recommended that she be treated immediately. I am of the opinion that if there are symptoms, we should treat them immediately and not let them remain in our bodies for 30 years.

Undiagnosed means that the patient had the symptoms, very pronounced symptoms, but the doctors simply did not think of it. Unfortunately, there were several such cases that lasted for years. Perhaps I can say that the longest case I know of was someone who had been injecting themselves with antibiotics intravenously for seven years because they thought they had Lyme disease or some kind of infection, but they tested positive with us, so this shows that it is not worth treating yourself.

DualDur can be used as a control before and after therapy, so the success of the treatment can be monitored. There is no other proven direct test that can detect the pathogen at any time and also provide accurate statistics on it, thus confirming the effectiveness of the therapy. By examining the results in detail, we can see the level of Borrelia and how the treatment has affected it. We have had several cases where, as we later learned, the attending physician or therapist requested tests before and after treatment, and we were able to help them with feedback on the direction of the therapy. Some doctors have modified their treatment plans based on our results and achieved success. There have been several cases where the patient was symptomatic before, the result was positive, and then, as a result of the otherwise proven combination treatment, the symptoms disappeared and DualDur became negative. However, there have also been cases where the therapist’s usual treatment was not effective and the symptoms and infection remained. After our colleague requested assistance, we were able to show that the treatment had only minimally reduced the level of the pathogen. Thanks to the consultation, the treatment was modified, and after a few months, the symptoms disappeared and the lab results became negative. Soon there will be enough data to describe a few case studies, and there has already been interest in clinical research from abroad.

We have already received samples from 32 countries, including Turkey and Australia, where the person travelled specifically to have this test done. However, samples are sent regularly on a weekly basis from about ten countries.

What further steps and developments await DualDur and Lyme diagnostics?

In order to develop a clinically validated device, each development step must be retested. This means that the data from clinical research is available and each new version must be researched again. Our developments so far have been about speed and usability, and we have now completed the development phase, where we have been able to develop a new and much better and more efficient system. It already works with several types of artificial intelligence models, so-called explainable AI. We have reached the point where it is understandable, even from a purely professional point of view, how artificial intelligence makes its choices and what are the main factors it measures and uses to make a diagnosis. So, our next clinical research is coming up.

More and more people want to involve us in clinical research to monitor treatment. Preparations for this are currently underway based on two or three different requests. One of them is very close to getting started.

We are currently at the stage where we can tell from the detailed test results which sample is most likely to contain the type of Borrelia that causes the infection, and based on this, we can plan antibiotic sensitivity. In five years’ time, we would like to be at the stage where we can extract the bacteria from a given patient’s sample and determine the most effective treatment option. So, from the field of precision medicine, where effective treatment can be recommended for a given patient group, we can move on to the field of personalised medicine, where we can help specific individual patients.