Measurement of IgG antibodies against the bacterium Coxiella burnetii does not reliably predict disease-related events or therapy failure during treatment and follow-up of patients with chronic Q-fever. Alternative markers for disease management are therefore needed. For the time being, management of patients with chronic Q-fever should be based on clinical factors, PCR test results, and imaging results. This was concluded in a Dutch study that has now been published in Clinical Microbiology and Infection.

Diagnosis and management of patients with chronic Q-fever is based on clinical factors, imaging results, and microbiological tests, including testing for IgG antibodies against Coxiella burnetii (the bacterium that causes Q-fever). However, although recommended in most management guidelines, measurement of antibodies might not be an adequate marker for disease activity since a quarter of patients have possible chronic Q-fever without evidence of chronic infection or a disease-related event. Nevertheless, they have persistent, high IgG antibody levels after their primary infection. In addition, IgG antibody levels vary within patients, also because its assessment is susceptible to measurement errors, and do not always seem to reflect the course of the disease. Therefore, investigators from UMC Utrecht, Radboudumc and Jeroen Bosch Hospital assessed the prognostic value of IgG antibody measurement in a retrospective cohort study using data from the Dutch Chronic Q-fever Database.

Not related to mortality or treatment failure
In total, 337 patients from academic as well as peripheral hospitals that were treated for proven/probable chronic Q-fever were included in the analysis. Of these, 264 had been treated for at least 1 year, most of them with doxycycline plus hydroxychloroquine. Complications occurred in 190 (56.4 percent), disease-related mortality in 71 (21.1 percent) and therapy failure in 142 (42.1 percent) patients.

From the analyses it appeared that IgG antibodies were not associated with a first occurrence of a disease-related event, defined as a new complication or chronic Q-fever related mortality after initial presentation (HR 1.00, 95% CI 0.86–1.15). IgG antibodies levels were also not associated with therapy failure, which was defined as a new complication or Q-fever related mortality after at least 12 weeks of antibiotic treatment and/or a new positive PCR test result after having been negative for at least 3 months and/or a persistent positive PCR test result for more than 6 months (HR 1.02, 95% CI 0.91–1.15).

Alternative markers needed
Principal investigator Jan Jelrik Oosterheert MD, PhD, internist-infectiologist at the Department of Infectious Diseases at UMC Utrecht, concludes: “In the largest cohort study so far, C. burnetii serology did not reliably predict disease-related events or therapy failure during treatment and follow-up of chronic Q fever. Therefore, we need alternative markers for disease management. Until such disease markers have been developed and validated, management of patients with chronic Q-fever should be based on the clinical symptoms, PCR test results, and imaging results.”

Jan Jelrik Oosterheert

Chronic Q-fever guidelines challenged
After infection with C. burnetii, chronic Q-fever develops in 1–5 percent of patients, often causing endocarditis or vascular infection. In general, long-term treatment with at least two antibiotic agents is indicated for patients with proven/probable chronic Q-fever, typically for a duration of 18–24 months. The results of this study nuance the current Dutch guidelines that recommend follow-up for 5 years for serum IgG and to strive for a 4-fold reduction of IgG antibody levels after discontinuation of antibiotics.

Expertise network
UMC Utrecht is a partner in an expertise network for the treatment of adult patients with chronic Q fever. The Wilhelmina Children’s Hospital is leading research into the chronic consequences of Q fever in children.

Publication
Buijs SB, Roeden SE van, Werkhoven CH van, Hoepelman AIM, Wever PC, Bleeker-Rover CP, Oosterheert JJ. The prognostic value of serological titres for clinical outcomes during treatment and follow-up of patients with chronic Q-fever. Clin Microbiol Infect 2021, in press.