Ixodes: exploration of a cell mediated immunity test for the early detection of Borrelia infection

Laboratory tests for Borrelia infection are diverse. They are subject to
discussions on interpretation and diagnostic value. Discussions in the
Netherlands ended in a CBO guideline published in 2013. This guideline does not
provide a solution for diagnosis of Lyme in an early stage, with the exception
of a clinical diagnosis based on development of a (strictly defined) Erythema
migrans (EM). Many infected people do not develop a characteristic EM. It is
therefore important to identify and develop alternative methods for diagnosis
of Lyme disease that are highly sensitive and sufficiently specific. In this
study a cell mediated immunity test will be investigated for this purpose.

The objective of the study is to develop a whole blood cell-mediated immunity
test for Borrelia infection and investigate whether such a test can detect
Borrelia infections more reliably than the currently used antibody tests in the
early stage of infection.

Subjects with a tick-bite in the previous 10 days will be recruited and tested
for Borrelia infection using standard serological tests and a cell-mediated
immunity test. Tests will be repeated 4 and 12 weeks after the tick-bite. Prior
infections will become apparent during the first measurement.
The difference in antibodies and cytokines between 1, 4 and 12 weeks will be
determined for each subject. At the same time clinical symptoms will be
reported using questionnaires.
At the end of the study the total number of infections will be determined. This
will allow calculation of the percentage of infections identified by serology,
CMI test or both.
Having sufficient infected and non-infected subjects will allow the generation
of a classification model, that will subsequently be used to predict the
infection status of subjects that only developed less characteristic symptoms.

Risks
The risks associated with standard blood drawing by a professional are
negligible.
Risks associated with testing for Lyme Disease are that a healthy subject may
be positive in the Lyme test indicating present or past exposure to Borrelia.
Considering the fact that there is a high background infection rate in the
Netherlands, this does not require specific actions, provided that the subject
is symptom-free and there is no indication for a recent infection. If a recent
infection is suspected based on seroconversion the GP will be informed.
Discovered in an early stage, Lyme disease can be effectively be treated with
antibiotics.

Benefits
The advantage of participation is that any subject testing positive for early
Lyme disease will be able to get treatment fast. His/her GP will be informed in
order to decide on medical follow-up. Considering the consequence of lack of
treatment, it is not possible to participate without consent on this point.
This will be registered in the informed consent form.