The principal goal of this study is to identify whether and how innate immune host factors predispose to the development of chronic Q-fever.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Aneurysms and artery dissections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Circulating cytokine profiles in serum of patients during different stages
of the various clinical manifestations of Q-fever.
2. In-vitro recognition and signalling pathways, cytokine pattern, Th-cell
differentiation and macrophage polarisation of peripheral blood immune cells
and immune cells isolated from aneurismal aorta wall, after stimulation with C.
burnetii components.
3. Immunohistochemical properties of immune cells in aorta specimens of
(Coxiella-infected) AAA patients and mRNA analysis for genes encoding proteins
involved in the recognition and signalling of C. burnetii.
4. Polymorphisms in innate and adaptive immune response genes that may be
related to the susceptibility and/or the development of a clinical
manifestation of Q-fever.
Secondary outcome
n.v.t.
Background summary
In the recent Q-fever outbreak in the Netherlands about 10.000 individuals have
been exposed to Coxiella burnetii, the bacterium that causes Q-fever. In 2-5%
of these individuals chronic disease develops, in which Coxiella burnetii
persists at endovascular foci causing endocarditis or mycotic aorta aneurysm,
or - in pregnant women - placentitis. Chronic infection with C. burnetii has a
poor prognosis. It is currently unknown which host factors influence Q-fever
susceptibility and the progression to chronic, life-threatening disease. We
hypothesize that host factors in immune response against C. burnetii are
important in development of chronic Q-fever.
Study objective
The principal goal of this study is to identify whether and how innate immune
host factors predispose to the development of chronic Q-fever.
Study design
A case-control study will be performed in the Radboud University Nijmegen
Medical Centre (RUN-MC). The duration of the study is 3 years. Patients and
controls will be recruited from the RUN-MC and collaborating hospitals. We will
use several approaches to investigate innate immune factors in Chronic Q-fever:
1. In sera from patients suffering from acute and chronic Q-fever, circulating
cytokines belonging to the T helper (Th)1, Th2, Th17 and T regulatory cell
types of response will be measured.
2. In-vitro experiments will be performed to determine the innate immune
response to C. burnetii systemically of peripheral blood cells from patients.
3. The same experiments will be performed to determine the innate immune
response to C. burnetii locally of immune cells in aneurismal aortic wall.
4. Genetic variations in the innate and adaptive immune response genes will be
assessed in DNA samples of individuals displaying the complete spectrum of
clinical manifestations.
Study burden and risks
Burden:
- For patients: collection of extra blood, if possible during regular blood
sampling. This comprises a maximum of 1 heparin tube à 5 ml and 4 EDTA tubes à
10 ml and 1 serum tube à 3.5 ml.
- For controls: the same as for patients, but blood sampling for the purpose of
this study only will be necessary in all cases.
- One specific group of newly diagnosed chronic Q-fever patients starting on
treatment (n=10) (part 2ii) collection of extra blood repeatedly during regular
blood sampling for follow up. This comprises 1 heparin tube à 5 mL at each 3
monthly control, plus 4 EDTA tubes à 10 mL at each 6 monthly control for a
maximum duration of 2 years.
Risks:
- No risks other than local hematoma are related to venous puncture.
- No risks are involved in obtaining the surgical specimens in
(Coxiella-infected) AAA or AOD patients. This will be rest material obtained
during open surgery of the aortic wall.
Benefit:
There will be no benefits for the subjects enrolled in this study.
Postbus 9101
6500 HB Nijmegen
NL
Postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Chronic Q-fever patients:
- Proven or probable chronic Q fever according to the recent consensus of the Dutch workgroup on Q-fever;Q-fever fatigue syndrome (QFS) patients:
- Laboratory-proven acute Q fever in the 3 years before presentation and/or positive serology fitting a past infection with Coxiella burnetii
- AND being severely fatigued, defined by scoring 35 or higher on the subscale fatigue severity of the CIS
- AND being fatigued for at least 6 months;Patients with past Q-fever infection without chronic infection or QFS
- A history of laboratory-proven acute Q-fever infection by either PCR on sera or serology fitting acute infection
- No chronic sequelae at least after 12 months of follow up;Healthy serologic negative volunteers:
- Negative Q-fever serology;Vascular patients with chronic Q-fever undergoing surgery for infected atherosclerotic aorta aneurysm (AAA) :
- Proven chronic Q-fever infection with infection of the vascular wall seen on CT, PET-CT or ultrasonography
- Necessity of resection;Vascular patients undergoing surgery, either with AAA or AOD
- For patients with uninfected AAA: An aneurysm of the aorta abdominalis for which resection with prosthetic replacement is necessary
- For patients with AOD: An obstructive defect in the aorta or iliacal artery for which resection with prosthetic replacement is necessary ;Seropositive individuals reporting no history of Q-fever
- Serology fitting past infection
- No reported history of acute Q-fever ;Seropositive individuals with a history of acute Q-fever
- A history of proven acute infection by either PCR on sera or serology fitting acute infection
- No chronic sequelae at least after 12 months of follow up;Seropositive individuals with QFS
- Laboratory-proven acute Q fever in the 3 years before presentation and/or positive serology fitting a past infection with Coxiella burnetii
- AND being severely fatigued, defined by scoring 35 or higher on the subscale fatigue severity of the CIS
- AND being fatigued for at least 6 months;Seropositive indivuals with chronic Q-fever
- Proven or probable chronic Q fever according to the recent consensus of the Dutch workgroup on Q-fever;Seronegative individuals (controls) living in the endemic area without a history of Q-fever
- Negative Q-fever serology
- Living in endemic area
Exclusion criteria
Age <18 years
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL35784.091.11 |