What do you think of the current situation and its medical, social, bureaucratic and legal implications?
Let’s focus on the medical aspects, as this is my field of expertise. Recently the ECDC reported on the validity of serological tests which turned out to be around 80%. It may be worse. The claimed sensitivity and specificity of the various tests range from 22% to 100%, which makes it hard to believe that any of these numbers is true. With a combination of serological tests we think that you can find that most people who do make antibodies. However, those patients without an antibody response will be missed by definition. The cellular tests such as the LTT and Elispot, and in the future hopefully the Ixodes test, will close that gap to some extent but may still miss part of the infected population.
The complexity leaves people that are ill with a straightforward question: “do I have Lyme?” “Are there antibodies?" "Is there T-cell activity?" "And if so, what does that actually mean?" People get utterly confused about test results and need to rely on their doctors to do a proper interpretation. But most doctors are not sufficiently aware of Lyme and the meaning of the tests to do that. The result is that the actual number of infections does not get reported, because doctors believe it cannot exist - based on the misinformation they receive.
When I started working on Lyme, I was pleasantly surprised how reproducible most serological tests are. The main drawback is that they see just part of the picture. Due to differences between the composition of tests and the interpretation of them. I have seen different manufacturers and doctors interpreting the same test result of one patient in opposite ways.
I have also heard doctors rejecting “German lab results” outright, but there are no “German labs” as a whole. The regular labs use the same methods as their Dutch colleagues. The labs in Augsburg, Neuss and Berlin are looking at a different part of the immune system, each using different methods. These different tests cannot be compared that easily. If one looks at antibodies, while the other looks at cell growth, how should one compare data?
Doctors want one simple cheap test that gives absolute certainty of the presence of a disease so it can be treated. That is hard with a complicated disease such as Lyme. People can have acute infections or older ones. Some infected people have a clear EM ring, while some don’t. They can have disseminated symptoms. There is no such thing as a ‘general Lyme patient’, so one has to be careful not to compare apples and oranges.
The complexity of diagnosis and treatment is comparable to the early stages of cancer research and treatment, when every cancer was regarded in the same way and only one type of treatment was thought of to kill all tumors. Now we know we need precise information and tailored treatment for cancer. Having worked for many years in a pharmaceutical company, I have seen the changes from a “one size fits all” therapy to precision medicine. This is generally accepted now for cancer and is much more effective. But somehow with Lyme, we are back to that same old mindset again. This does not make any sense to me.
With the current mindset that most doctors have towards Lyme and the pressure of insurance companies to have certainty in order to pay, this leads to a very unfortunate situation for the patients. People are suffering, also after two weeks of treatment. Since we cannot yet measure the presence of Borrelia reliably, the scientific evidence that the infection is gone and will not return after 2 weeks of oral antibiotic treatment is just as hard to find as the opposite.
At some point I learned from a doctor, that they are worried about over-treating people. If serious side effects emerge (which is not unlikely with antibiotics) they may face charges for misconduct. That helped me to understand their position better. However, if it is unclear what an active infection is, what damage has been done by an older infection and whether the infection is persistent, you do not tell your patients to see a psychologist. You continue looking at options for different kinds of treatment.
With acute infections two weeks of doxycycline may be sufficient, but with older infections I find it hard to believe that it is sufficient. Doxycycline does not get into the brain so for neuroborreliosis you may need a different drug or different combination of drugs. In case of persistent infections in Q-fever, treatment with doxycycline and Plaquenil goes on for at least eighteen months. Thus, long term antibiotic treatment is not forbidden in general.
We are still in the infancy stage in understanding the disease. The fact that this is not frankly admitted leads to dramatic situations. I knew Gerard de Bruin, who died in 2015, quite well and understood why he decided to end his life. This drives me in my efforts to come up with something better.
The second Under our Skin documentary featured the Norwegian professor Motzfeldt Laane, who claimed to have found a way to find the Borrelia under a microscope. There are also experts who claim that Lyme is transmitted in multiple ways, including during pregnancy or via blood transfusion. Why did you chose to measure antibodies to determine infection and use only people recently bitten by a tick as your population for the Ixodes study?
There simply is no Golden Standard now, so we need to work with what we have, within the budget and with the partners who are willing to cooperate and are open-minded enough to advance. Validation is a process of making choices and using your scientific expertise and common sense.
We did look at microscopy. The problem with many papers is that observations are limited to one institution. To be considered valid different groups need to show that the method works. Since Dr. Motzfeldt Laane’s work did not receive any follow-up, it is hard to judge how valid his method is.
The set-up of scientific research does not allow the inclusion of too many uncertain factors. Validating a new test based on another non-validated test is not possible. So we have chosen for this approach and this group of people with a high risk of infection to make the research work.
For the further development of the Ixodes test, we work together with European partners. I know that some people are skeptical of the involvement of dr. Stanek of the University of Vienna in our consortium, because of his role in the IDSA. I was actually pleasantly surprised by how open-minded he is, and how interested he is in novel approaches to diagnosing Lyme. The first thing he told me was that he realizes that the current antibody tests have their limitations. We simply need to and want to work with key opinion leaders like him, to have enough leverage to get things done.
With regard to other ways of transmission: for our work on a better test however, that does not matter. If a large enough group of people have recently been bitten by a tick, their blood samples can tell us over time if we are on the right track for the development of our new test. For Lyme to be an urgent health issue, we also do not even need to look at other ways of transmission. Last year 1,5 million people reported to have been bitten by ticks last year in the Netherlands. With the current state of affairs, anyone can become a Lyme patient tomorrow.
Where do you see room for improvement?
First of all, money. Three years ago the Dutch minister of Health initiated the formation of a Lyme Expert Center. One million dollar for additional research on Lyme was allocated. This amount is extremely low compared to the money that is invested in cancer research. As a comparison: in 2016 the sponsor event at Alpes d’HuZes generated in eleven million euro in one day. So one million euro can be considered merely as window dressing. This amount of money will not lead anything substantial.
Just compare it to the EU, which invests nearly two million in one project! To have impact, ten times that amount would be a good start. Spending some money on dissemination of information and initiatives by patients could be done better. The experts need to get out of their ivory towers, improve education of GPs, cooperate with other parties and improve the quality of the public conversation.
Much of the public health communication is now focused on “prevention of tick bites” and on “not creating panic”. As an example, when we started our study we ran into the problem that organizations did not want to spoil peoples pleasure on vacation. That clearly changed in the second year of the study. Good information also allows for making people aware of risks, so they can manage them.
Secondly, more parties need to be recognized as Lyme experts. The discussions lead by ZonMW with all stakeholders were very open. At the end, however, the three parties that are the basis of the Lyme Exert Center did not want to sign the Action Plan. Later on they still committed to the Action Plan Lyme and received funding for their research, but it was strange that these parties were holding back rather than moving forward and leading the way.
For the Lyme Expert Center, I would have liked to have one physical ‘learning space’ in the middle of the country, where all involved are welcome and where we can actually test and treat people, to learn from each other. That includes learning from the patients themselves.
I would also like to see GP-lead Lyme centers in every major region of the Netherlands with nurse practitioners that recognize a red ring, and GPs that understand the value of the different diagnostic tests. If this would be funded from the standard basic insurance the costs will be much lower that when specialists and hospitals are involved. More efficient diagnosis and better treatment in the early phases of disease will prevent chronic cases. Why wait till people get infected and so ill that they need an academic hospital?
Finally, the guidelines for diagnosis and treatment of Lyme need to be updated as soon as possible to the latest scientific standards and need to take into account that there is far less certainty now than policy makers would like to have. This would allow for more consideration for the patients, more monitoring by GP's when people get treatment from specialists in the Netherlands or abroad, less suffering, cuts from disability payment because of ‘negative’ test results that are difficult to interpret.
What do you think of the recent news about the trouble parents of Lyme face with the government?
I followed the news on the actions taken against parents that take their children abroad for treatment for Lyme and how negative test results play a major role in them. How can anyone be so sure to take away children from their parents, if so little is known? This recent discussion really baffled me, not specifically as a professional, but rather as a mother.
To the paediatricians working for Child Protection Services I would suggest to look into the mirror and ask themselves if they would want to be treated like this, when their children become sick with Lyme Disease. Since this may happen tomorrow, would you want to be treated as these parents are treated? I do not think so. Let’s learn from that.
Note from the interviewer: professor Motzfeld Laane was fired after he spoke at the Norvect Lyme conference in Oslo in 2014. In a personal communication, he told us that not only his university lab was closed down, but that the online scientific Journal that published his research paper was hacked so badly, it stayed offline for years. We will soon publish the original text of his article and new information he sent us on the Research section of our website.
This blog post is based on a 2,5 hour interview on February 22, 2017