T cell Response in Q fever (TRIQ-study)

Q fever is an emerging zoonosis in the Netherlands with more than 4000 human
cases since 2007. Acute disease is followed by clinical resolution in the
majority of cases, 1-5% of patients progresses to chronic disease and 10-20%
will exhibit the post-Q fever fatigue syndrome (QFS). Little is known about the
pathophysiological mechanisms underlying these different clinical outcome
states and current diagnostic tests measuring the humoral immune response (CFT,
IFA, ELISA) to Coxiella burnetii infection have considerable limitations in
accurately diagnosing these clinical outcome states. For example, diagnosing
QFS relies solely on patients symptoms, as serological results do not differ
from those asymptomatic after reconvalescence. Furthermore, establishing a
diagnosis of chronic Q fever can be quite challenging due to lack of validated
cut-off values for commercially available serodiagnostic tests. A recently
developed paradigm postulates clinical outcome after Coxiella burnetii
infection to be dependent on host-immunity/pathogen interaction. In this
pathophysiological model, strong emphasis is given to persistence of Coxiella
antigens in the host (as viable Coxiella bacteria in case of chronic disease,
or remnant coxiella antigens in QFS), and dysfunctional host cellular immunity.
T-cell mediated cellular immunity has a pivotal role in dealing with primary
Coxiella burnetii infection and subsequent clearance or control of the
bacterium in the host. Therefore, determining T-cell responses in Q fever
patients can provide insights into the pathogenesis of the different Coxiella
burnetii infection clinical outcomes. Furthermore, such a test may aid the
clinician in accurately diagnosing the outcome of a Q fever infection and might
be useful in guiding therapeutic interventions.

Primary Objective:
To determine T cell response to Coxiella burnetii antigens using an ELISPOT
interferon gamma release assay in patients with different clinical outcomes
after acute Q fever

Descriptive study, evaluation of a new diagnostic test.

Both volunteers and Q fever patients will undergo a full history and physical
examination, fill out a questionnaire and will be subjected to a single blood
sampling. No specific risks are associated with any aspect of the study.