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Tick-borne diseases are the most prevalent vector-borne diseases in Europe, and are predicted to further rise in the near future. Tick-borne diseases other than Lyme borreliosis and tick-borne encephalitis have been largely neglected and knowledge on their incidence and clinical presentation is minimal due to the lack of awareness and diagnostic tests. We have mounting published and unpublished data that Dutch people are frequently exposed to, and infected with, other tick-borne pathogens, such as Borrelia miyamotoi, Anaplasma phagocytophilum, Neoehrlichia mikurensis, as well as Babesia and Rickettsia species. With over one million tick bites per year in the Netherlands, 30% of ticks being infected with another tick-borne pathogen, increasing incidences of ticks and tick-borne diseases in Europe, and also our recent discovery of tick-borne encephalitis virus in Dutch ticks, roe deer and humans, there is a need for awareness, knowledge, diagnostic tests and clinical case definitions for all tick-borne diseases, not only for Lyme borreliosis.

 

Therefore, in a multidisciplinary and collaborative effort between primary care, academia and public health we will aim to:

 

1) Improve supportive diagnostic tools for the diagnosis of other tick-borne diseases.

 

We will develop and test molecular and serological tests that are based on European isolates/strains of the various TBPs. To this end, we will make use of European isolates of other tick-borne pathogens and a unique collection of sera from patients with other tick-borne diseases and controls that are available within the institutes of the project team and collaborating partners;

 

2) Study the incidence of other tick-borne diseases in selected patient groups in the Netherlands.

 

We will perform both retrospective analyses and a prospective clinical study and we will use the improved diagnostic tools (point 1). These studies will gain insight into the incidence, clinical characteristics and impact of other tick-borne diseases in the Netherlands. Both retrospectively and prospectively we will perform clinical studies to assess the incidence of tick-borne diseases. The focus of this Key Objective will be on patients with a febrile illness after a tick bite. Archived sera from well-documented patients are available through sera collections of the institutes of the project team and collaborating partners and will be retrospectively tested for antibody responses against tick-borne pathogens. In addition, patients with acute febrile illness after a tick bite (to a maximum of 4 weeks) will be enrolled through www.tekenradar.nl in a prospective setting. This website has proven successful as an inclusion platform for two earlier ZonMw-funded clinical studies on tick bites and tick-borne diseases. At enrollment, acute febrile patients will be screened and patients will only be invited for the study if other etiologies than TBP infection are unlikely (through screening by questionnaires and a telephonic interview). After inclusion and informed consent blood samples and online follow-up questionnaires will be taken and if the participant has consented the treating physician is contacted for additional information. Detection of (antibody responses against) tick-borne pathogens in the “tick bite followed by fever” cases will be compared to detection in controls that reported a tick bite not followed by fever, and healthy controls. Since a preliminary analysis reveals that fever is reported after 3-6% of tick bite reports on www.tekenradar.nl, and 10.000 tick bites are reported on this website each year, we expect to enroll at least 600 cases in 3 years.

 

3) Establish case definitions and a national guideline for the diagnosis, treatment and management of other tick-borne diseases in the Netherlands, raising awareness for other tick-borne diseases and providing guidance for (primary) health care professionals.

 

As part of this Key Objective the established infrastructure, methodology and network of the National Coordination Center for Communicable Disease Control (RIVM-LCI) will be used. The results from the studies described above (point 1 and point 2) will form a strong basis for, and increase the impact of, the case definitions and guideline.

 

Thus, our project will aid in the understanding of the medical and societal impact of other tick-borne pathogens and tick-borne diseases, and will boost the knowledge, awareness and diagnostic support for other tick-borne diseases amongst the public and clinicians. Importantly, we will also generate clear-cut and tangible results, such as new diagnostic tests, case definitions and a new guideline, which will be directly implemented into daily clinical practice. This will be informative and useful for the public, as well as health care professionals, and will thus lead to an improved case detection and management of patients that have been exposed to tick-borne pathogens.

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