Improving the management of tick-borne diseases in the North Sea Region

21 December 2021 - Published by Per-Erik Lindgren

Joppe Hovius is an infectious disease specialist and the founder of the the Amsterdam UMC Multidisciplinary Lyme borreliosis Center. Amongst other activities, this center provides patient-oriented, high-quality care to patients suspected of having Lyme borreliosis or other tick-borne diseases. He is also a member of the NorthTick consortium as well as principal investigator of several other research projects  on ticks and tick-borne diseases.

What is your role in the Northtick project and why did you become interested in tick research in the first place?

I am the activity leader of several activities in work package 4 (aiming to improve the diagnostics of tick-borne diseases) and work package 5 (striving to improve the management of those suspected of a tick-borne disease). My interest in ticks and tick-borne diseases stems from many years back. As a medical student I did an internship at Yale University, close to Old Lyme, Connecticut, USA, after which the disease was named. Later, during my PhD, I focused on the molecular interactions between the tick, the pathogens it transmits and the host defense mechanisms. After I specialized as an internist-infectious disease specialist i founded the Amsterdam UMC Multidisciplinary Lyme borreliosis Center.

Could you tell us more about the outpatient clinic at AMC?  Who are the patients who are referred, and why is it necessary to study this patient group?

At our specialized outpatient clinics at Amsterdam UMC Multidisciplinary Lyme borreliosis Center, we annually see hundreds of individuals that are suspected of a tick-borne disease, mostly Lyme borreliosis. Depending on the type of complaints patients can be evaluated by an infectious diseases specialist, neurologist, dermatologist, rheumatologist or in the case of children by a pediatrician. We are a tertiary center and get referrals from all over the country and sometimes even abroad. Since, in the Netherlands, many clear-cut cases are oftentimes diagnosed and treated by general practitioners or in regional hospitals, the population we see at our outpatient clinics is highly biased. I want to emphasize that, regardless of the underlying diagnosis, many of the patients we see have debilitating and long-lasting symptoms. Of such patients, a relatively large proportion, at least according to our criteria, but always after a thorough evaluation, do not have evidence of (active) Lyme borreliosis. For a substantial number of such patients we have been able to establish an alternative diagnosis. On the contrary, we also have examples of patients that have visited multiple physicians without a classifying diagnosis, in which we could readily diagnose Lyme borreliosis. This underscores that the diagnosis of Lyme borreliosis can be a t(r)icky business. We have published on the experiences and findings at our outpatient clinic in 2015 (Coumou et al. CMI 2015) and we, in collaboration with another academic medical center in the Netherlands (Radboudumc), have recently initiated a biobank, so we will surely study this in more detail in the future.

In NorthTick you are also involved with work on the management of tick-borne diseases in the north sea region. Is there a lot of differences between the North Sea countries? In what areas is there room for improvement?

There are surely differences, but also a lot of overlap. We have recently published an overview (Kullberg et al. BMJ 2020), which highlights some of these differences and provides an overview of generally accepted aspects of Lyme borreliosis diagnostic and treatment. It also underscores that every patient deserves a thorough evaluation as to whether their complaints are caused by Lyme borreliosis. In addition, in case of persisting symptoms after receiving recommended antibiotic treatment for Lyme borreliosis, the work-up should include a search for an ongoing infection or inflammation, residual damage or post-infectious symptoms, amongst other causes.

An interesting difference is the use of intravenous antibiotics (ceftriaxon) in the Netherlands to treat Lyme neuroborreliosis, yet oral antibiotics (doxycycline) in Scandinavian and other countries are used to treat the same condition. Although the evidence in favour of oral doxycycline to treat this serious Lyme borreliosis manifestation is mounting, I think this is something that should be studied at a European level. This asks for collaboration between various European countries and would require specific funding.

Evidence for persistent Borrelia infection after antibiotic treatment in humans is sometimes extrapolated from findings in animal models for Lyme borreliosis. This is also used by those advocating long-term antibiotic treatment of patients with chronic symptoms attributed to Lyme borreliosis. But, is that evidence solid, and how can the findings from animal models be translated to the human setting?

We are currently reviewing all data on this topic from the most often-used animal models (i.e. mice, dogs and non-human primates). Without wanting to reveal too much of our findings I can, in general, say that one should be careful to extrapolate findings from animal models directly to humans. How these studies were set-up, what type, administration routes and dosages of antibiotics were used, and how was persistent infection measured are factors that should be taken into account. In addition, regardless of the findings in animal models, there are multiple human placebo-controlled trials that show no substantial or long-lasting effect of longer antibiotic treatment (with the usually recommended antibiotics) in patients with chronic symptoms attributed to Lyme borreliosis. Therefore, whether a patient with chronic symptoms attributed to Lyme borreliosis requires (re)treatment should be carefully considered for every individual patient, and that is what we try to do at the Amsterdam UMC Multidisciplinary Lyme borreliosis Center.