Anti TNF therapy and susceptibility for Coxiella burnetii infection

From 2007 on 4000 cases of acute Q fever are reported. As acute Q fever is
often asymptomatic, the actual number of people infected with Coxiella burnetii
is expected to much higher. 1-5% develops chronic Q fever, of which
endocarditis and vascular (graft) infections are the most common
manifestations. Morbidity and mortality are high, if left untreated. It is
stated that immunocompromised patients are at elevated risk for the development
of chronic Q fever, although this disease entity was not well defined and
statistical evidence is lacking. The risk of rheumatoid arthritis (RA),
arthritis psoriatica or Bechterew disease, and the use of TNF-alpha blockers in
particular, for the development of chronic Q fever is not assessed. Although
in-vitro studies have been controversial about the role of TNF-alpha, the
hypothesis is that TNF-alpha blockers increase the risk of development of
chronic Q fever.

1. To determine, in patients treated with TNF α blockers and living in the
Q-fever endemic area, the prevalence of antibodies against C. burnetii and the
prevalence of chronic Q fever.
2. To assess other determinants in this group of patients which predispose to
chronic Q fever disease.
3. To assess, in a subset of patients treated with anti-TNFα blockers, the
influence of this therapy on the production of cytokines by white blood cells
exposed to C. burnetii.
4. To assess, in a subset of patients treated with TNF α blockers, the
influence of this therapy on monocyte/macrophage function reflected by
macrophage polarization and cytokine production upon exposure to C. burnetii.
5. To determine whether positive serology or the serology proving chronic
Q-fever is associated with the presence of genetic polymorphisms influencing
the immune response towards C. burnetii.

1. Observational, case- control, case-finding study
2. In-vitro laboratory study
3. Genetic analysis

All participant are asked for blood samples and to fill in a questionnaire and
an informed consent form for the Q fever screening and the genetic part of the
research. In a subset of patients (n=24) an extra blood sample will be asked
for the in-vitro tests.
Possible benefit is early detection of chronic Q fever, with the possibility to
prevent severe morbidity and mortality.