New insights in the development of Q fever fatigue syndrome Abnormalities in the immune system provide more insight into the disease

People with Q fever fatigue syndrome have abnormalities in their immune system compared to healthy people. Ruud Raijmakers conducted research into various elements of Q fever fatigue syndrome, including the role of the central nervous system and cognitive behavioural therapy as a treatment. He will receive his doctorate on Wednesday, December 8.

Q fever is an infectious disease caused by the bacterium Coxiella burnetii. The disease is transmitted from animals to humans (zoonosis), often via goats or sheep. The bacterium mainly spreads through the air. When people become infected with C. burnetii, around 40% develop flu-like symptoms that are sometimes accompanied with pneumonia or hepatitis. This is called an acute Q fever infection. During the Q fever outbreak from 2007 to 2011, tens of thousands of people became infected with C. burnetii and over 4,000 cases of acute Q fever were reported. Q fever has two long-term complications: chronic Q fever, a deadly disease that is characterised by a persistent infection with the bacterium, and Q fever fatigue syndrome (QFS), in which people retain long-term (fatigue) symptoms following an acute Q fever infection even though the bacterium has been cleared.

Fatigue and high burden of disease

Over 20% of acute Q fever patients develop long-term symptoms, such as fatigue, muscle ache, joint pain, headaches, night sweats, and rapidly recurring upper respiratory tract infections. The diagnosis QFS can be made if the fatigue persists for more than six months and there is no other explanation for the complaints. Why some patients develop QFS and others do not is unknown. Within the Radboudumc Q fever Expertise Centre, PhD student Ruud Raijmakers has been researching QFS for the past few years. Raijmakers: "We still know relatively little about infectious diseases that cause chronic fatigue. That is why I researched different aspects of QFS; the body seems to be out of balance in several areas."

Long-term Effects of Cognitive Behavioural Therapy

Among other things, Raijmakers investigated the long-term effects of cognitive behavioural therapy, a treatment that focuses on thoughts and behaviour that perpetuate fatigue. This treatment is known to benefit patients with chronic fatigue syndrome (CFS), a condition with similar symptoms. Raijmakers: "Our research has, strikingly, shown that the beneficial effects of the therapy wanes off sooner than expected in QFS patients. We don't know exactly why this happens, but it may pay off to tailor the therapy more to QFS and to schedule 'maintenance' or 'booster' sessions."

Abnormalities in first-line immune cells

In addition, Raijmakers looked at the origins of QFS. In the immune system, he found abnormalities in the first-line immune cells, the monocytes. These behave slightly differently in QFS patients than in people without QFS; for example, two genes responsible for the production of essential proteins are less expressed. "Since the proteins that are coded by these genes are involved in protecting cells, inhibiting inflammation, controlling metabolism and recovery after exercise, it is worthwhile to further investigate the role of these genes," Raijmakers argues in his thesis. "This has the potential to connect existing theories about the pathophysiology of chronic fatigue."

As for QFS, there is still much work to be done. According to Raijmakers, larger and better studies are needed to increase our knowledge about the disease, for example on the theory that QFS is caused by inflammation in the central nervous system (neuroinflammation). "We were unable to confirm previous results by a Japanese group that found signs of neuroinflammation in CFS. There are now better research methods, so a follow-up study on this would be of great value."

Although he has now started his training as a general practitioner, he wants to remain involved in research into post-infectious fatigue syndromes such as QFS. Raijmakers: "I have seen and worked with many QFS patients. There is still a lot we can do to help them. I hope to contribute to a better understanding of this syndrome and thus a better understanding for patients with chronic fatigue."

About the PhD

Thesis 'Immunopathology of Q fever fatigue syndrome' by Ruud P.H. Raijmakers. Supervised by: Prof. Dr. J.W.M. van der Meer, Prof. Dr. L.A.B. Joosten and Prof. Dr. C.P. Bleeker-Rovers. The defense takes place on December 8 at 10.30 am and can be followed live here.

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