The Qure Study: Q-fever Fatigue Syndrome - Response to Treatment

Q fever fatigue syndrome (QFS) is one of the most frequent sequelae of Q fever, and constitutes a significant problem in the current outbreak of Q fever. QFS leads to substantial morbidity and has a high socio-economic burden, related to increased use of healthcare facilities and absence from work. It is envisaged that over 750 patients will become chronically fatigued due to Q fever in The Netherlands (20% of 4000 patients from 2007 until now). Although the outbreak appears to diminish, it is expected that Q fever will remain an endemic disease, and therefore this number will continue to grow. A vast medical consumption can be anticipated, stressing the need for an accessible and effective intervention and clear treatment guidelines.

The study will contribute to a better understanding of effective treatment of QFS, providing evidence-based guidelines for general practitioners and medical specialists.

Inclusion criteria

• Males or non-pregnant, non-lactating females who are 18 years or older
• Laboratory-proven acute Q fever since the year 2007 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;
• AND disabled because of the fatigue, defined by scoring 450 or higher on the SIP
• Subjects must sign a written informed consent form.

Exclusion criteria

• Fulfilling criteria for chronic Q fever, namely:

• IFA IgG fase I ≥ 1024, ≥ 3 months after acute Q fever and/or
• Positive Coxiella burnetii PCR on serum or tissue, 1 month after acute Q fever
• Acute Q fever in the setting of a prosthetic cardiac valve or aneurysm surgery or stenting necessitating prophylactic use of doxycycline;
• Pregnancy or unwillingness to use effective contraceptives during the entire study period;
• Imminent death;
• Inability to give informed consent;
• Allergy or intolerance to doxycycline;
• Somatic or psychiatric illness that could explain the chronic fatigue;
• Subjects who are currently enrolled on other investigational drug trials or receiving investigational agents;
• Receiving antibiotics for more than 4 weeks, potentially active against Coxiella burnetii, for any other reason since Q-fever diagnosis;
• Subjects who are receiving and cannot discontinue barbiturates, phenytoin, or carbamazepine (these drugs may increase the metabolism of doxycycline and therefore reducing half-life of doxycycline);
• Moderate or severe liver disease (AF, ALAT, ASAT > 3 times the upper limit of normal).
• Current engagement in a legal procedure concerning financial benefits (only current involvement interferes with the effectivity of cognitive behavioral therapy. Once the appeal procedure ends, subjects can be included)