Q Herpen II, Post outbreak screening in a Q fever high incidence area for late consequences of Q fever including chronic Q Fever.

Between 2007 and 2010 the province of Noord Brabant, the Netherlands
experienced the largest Q fever outbreak described in the world. The number of
notified cases (acute symptomatic cases) according to the national notification
records, exceeds 4.000. Chronic Q fever and Q fever fatigue syndrome (QFS) are
serious sequels of acute infection documented among notified cases. However,
the large majority of people with an acute Coxiella burnetii (C. burnetii)
infection present no symptoms or only mild illness, for which they seek no
medical care. The risk for chronic infection in this group is unknown but
patients diagnosed with chronic Q fever in the Netherlands often lack a history
of acute illness. Therefore it is possible that chronic infections remains
undetected until serious illness occurs.

The village of Herpen in Noord Brabant experienced the first large Q fever
outbreak in the Netherlands. An earlier study in this village in 2007, just
after the first outbreak, found that 16.5% (73/443) of participants had -
unbeknownst to them - recently been infected with C.burnetii.

General practitioners (GP*s) and Q-uestion (patient organisation of people that
have been infected with Q fever) repeatedly expressed their concern that Q
fever infected individuals (even though their initial infection was
asymptomatic) might suffer chronic Q fever or other morbidity caused by Q
fever. If this is indeed the case or not can only be established through
further research. These groups were instrumental in requesting further research
and were from an early stage involved in the conception of this study idea and
fundraising.

In the present Q-Herpen II study this village (population 2.820) will serve as
a sample population for the Q fever stricken population in Brabant. Screening
the adult population in this village with a high Q fever incidence regardless
of their Q fever status- will enable us to identify patients with possible
chronic Q fever or other Q fever related morbidity. These participants are
unaware that they are at risk as their past Q fever infection was asymptomatic
/undiagnosed.

This study will provide a robust estimate of the prevalence of C. Burnetii
exposure and possible chronic Q fever among asymptomatic participants. This is
important in order to assess whether population screening in a high incidence
area is useful and should be expanded to other areas. Furthermore these study
data will establish whether asymptomatic/mild C.burnetii infection has an
effect on the health status and fatique status as measured with the NCSI
(Nijmegen Clinical screening instrument) a standardised instrument for the
health status (includuing the fatigue status) and the EQ-5D (a standardised
instrument for use as a measure of health outcome http://www.euroqol.org/ )

Another objective is to provide clarity where uncerntainty reigns. Hopefully
this thorough study will put worries and concerns to rest.

An adequate diagnosis, even after 6 years, will result in referral to a
specialist centre and, if needed, treatment and monitoring.

A cross sectional population-based study among the adult inhabitants (18 and
older) of a Q fever high incidence area. The sample high incidence area is the
village of Herpen (postal code 5373; total population 2.820) in the
municipality Oss. Based on data of the municipal administration all
approximately 2.200 inhabitants - age 18 and older - will be posted a
questionnaire on awareness of their Q fever status, Q fever testing history,
underlying disease, risk factors, and health status (NCSI and EQ5D).
Participants receive a laboratory form for one venipuncture for 2 test tubes
(10 ml) (tests IFA and IFNg=Q-Detect) together with an invitation with an
proposed day and time for blood drawing at a location in the village.The GGD
(Municipal Health Service) will offer six blood drawing opportunities over a
period of one week.
For those that were unable to participate during the first round a second and
last opportunity will be offered 3-5 weeks later with two blood drawing
sessions. Tests are offered free of charche.

An adequate diagnosis, even after 6 years, will result in referral to a
specialist centre and, if needed, treatment and monitoring. Furthermore we will
compare the Health Status (including the fatigue status using the NCSI
(Nijmegen Clinical screening instrument ) and EQ-5D (a standardised instrument
for use as a measure of health outcome http://www.euroqol.org/ ) for the of
participants in this sample.

Data are analysed in SPSS and corrected for confounders, age, sex, SES,
underlying disease, smoking etc.

The burden for participation consists of;
1. Filling out a questionnaire (10 to 35 minutes- after testing) (sent by post)
on the participant*s awareness of his/her Q fever status, Q fever testing
history, underlying disease, risk factors, and health status.
2. Donation of two blood samples (6 and 4 ml respectively) during one
venipuncture, during one visit to a convenient location in the village.
The venipuncture will be executed by trained staff and poses a minimal burden
and no significant risks.

Benefits
Patients with an IFA suggestive of possible Q fever will require further
examination. Since not all patients with a high IFA have proven chronic Q fever
this may cause psychological discomfort due to uncertainty of the final
diagnosis. A high/low IFA value in combination with a low or high IFNg
response, will aid the diagnosis *possible* Q fever.
The benefit for participants is that those with an asymptomatic chronic
infection are identified and referred to a specialist centre.