Pilot study to evaluate the potential value of Fluorescence In Situ Hybridization (FISH) of white blood cells for the diagnosis of Q fever fatigue syndrome

Q fever fatigue syndrome (QFS) affects approximately one in five patients
following symptomatic acute infection with Coxiella burnetii. Diagnosis of QFS
is complicated and criteria include a proven prior Q fever infection and
exclusion of other fatigue-associated somatic or psychiatric disorders or
chronic Q fever. Recently a preliminary report was published observing higher
levels of C. burnetii 16S rRNA in white blood cells of QFS patients compared to
healthy controls using a Fluorescence In Situ Hybridization (FISH) based test.
To be of potential value as a diagnostic tool for QFS, this test needs to be
able to clearly distinguish QFS patients not only from unexposed controls, but
also from individuals with a past asymptomatic infection and no subsequent
clinical sequelae.

To evaluate whether Fluorescence In Situ Hybridization (FISH) on blood cells
can distinguish patients with QFS from controls with no evidence of past
Coxiella exposure and individuals with past asymptomatic C. burnetii infection.

Forty-five subjects with known exposure history and clinical Q fever status
will be recruited for this single site observational case-control pilot study.
To ensure correct assignment of study groups, subjects recruited into groups A
and B will be asked to provide information on any relevant major changes in
their health status since 2014 that would pose a risk for the development of
chronic Q fever or OFS. Subjects recruited for group D will be asked for
consent to contact their treating physician to clarify they meet all criteria
for proven chronic Q fever. After inclusion, blood will be collected by
venipuncture at a single time point (max. 12 mL EDTA/lithium heparin blood and
8.5 mL serum). Per subject, two duplicate tubes of blood will be collected for
FISH analysis. The test laboratory will be blinded to the assessment of
duplicates and the (group) identity of subjects.

Venipunctures are performed by trained phlebotomists and pose a negligible
risk. Participation will require a one-time visit of max. 20 minutes. There are
no other procedures or follow-up after the specimens are obtained. Benefits for
subjects from group A include an additional measurement of their Q fever
exposure status (by IFA and IGRA). Participating individuals from group B, C
and D have no added benefit from the FISH test performed, since it is not a
validated diagnostic assay and their clinical status (past asymptomatic Q fever
infection; diagnosis of QFS or chronic Q fever) is already known to them.