General information on Hilysens II Project for clinicians

Borrelia is a pleomorphic bacterium with a complex life cycle that comprises a multitude of forms, including corkscrew-shaped "parent" forms and "cyst" forms that lack a cell wall, among others.
The lack of a bacterial wall makes it very difficult to detect by common imaging techniques, such as light microscopy, as well as by standard serological tests, since they trigger a different immunological response.
As a result, these Borrelia infections are very difficult to diagnose and treat, so that they persist in the body over long time periods, causing chronic disease.

According to the symptoms and the length of illness there are three stages of Lyme Disease:
stage I - localized skin infection (“bulls eye rash” or EM)
stage II - disseminated infection is characterized by inflammation of different organs weeks up to months after the transmission of Borrelia
stage III - persistent infection, with chronic inflammation of different organs and systems for longer than a year.

Common symptoms of Lyme Disease include flu‐like symptoms, aching joints, headache, gastrointestinal problems, light/sound sensitivity and malaise, although the range of symptoms is very variable among patients: some have only skin infections while others only develop late manifestations, such as arthritis.
Furthermore, Borrelia burgdorferi has been implicated in much more severe clinical manifestations, such as neocortical borreliosis (neuroborreliosis), which has been associated with Alzheimer’s disease.

Since only around 60% of patients develop the characteristic Erithrema migrans and just about 25‐30% recall the tick bite, diagnosis in the remainder of the cases requires confirmation by laboratory tests.
The harmful late‐stage effects of this disease are a consequence in part of the lack of sensitive and efficient diagnostic tools that are able to detect the disease in the early stages when it is easily tractable and to detect in a specific manner late (chronic and autoimmune‐related) infections.
To date, there is no available diagnostic tool that is able to detect in a sensitive and specific way the immunological response to the CWD forms of Borrelia, which is thought to be responsible for the chronic severe symptoms of borreliosis.
These forms present an altered protein expression pattern, as well as differences in antigen presentation compared with the parental form.
As a result, they are undetectable with current commercial methods based on whole‐cell lysate antigens of the Borrelia parental form.

Moreover, lack of diagnosis results in underestimation of disease prevalence and health risks, leading to critical delays in starting awareness and preventive policies.
Therefore, there is a crucial need to develop a sensitive tool for laboratory diagnosis of Borrelia burgdorferi acute and chronic infections to provide novel treatment options for patients suffering from their harmful infestations.

Based on the market needs, two main required features are clearly identified:
1. To improve on the current WB technique, which is very labor‐intensive, time-consuming, and difficult to standardize, the new tool should be robust, easy‐to‐use, and enable unambiguous interpretation of the test results.
2. To avoid the need for two different tests to secure a diagnosis and allow chronic infections to be detected, new antigens that have been reported in the literature in the last years but have not yet reached clinical use should be included.

With these premises in mind and with the input of all the project partners, the HILYSENS consortium set the goal of developing:
A highly‐sensitive, specific and robust diagnostic tool for Lyme Disease that is easy to use and interpret by frontline physicians and clinical laboratories and that will become the standard detection tool, rising awareness of this disease among European clinicians and permitting accurate quantification of the increasing disease incidence in order to carry out prevention campaigns before the disease becomes epidemic.