Q fever antibody does not predict disease progression

Measurement of IgG antibodies to the Q fever bacterium Coxiella burnetii has no predictive value for mortality, complications or therapy failure during treatment and follow-up of patients with chronic Q fever. Alternative markers for treatment and therapy success are therefore needed. This is shown in a study jointly conducted by the Radboudumc, Jeroen Bosch Hospital and UMC Utrecht.

Doctors should, therefore, for the time being base the treatment of patients with chronic Q fever on clinical symptoms, PCR test results and imaging results. This is according to a Dutch study now published in Clinical Microbiology and Infection.

Diagnosis and treatment of patients with chronic Q fever is based on clinical symptoms, imaging results and microbiological tests. These microbiological tests include the PCR test, which measures the amount of Coxiella burnetii bacteria (the bacteria that causes Q fever) in the blood. In addition, testing is also done for the presence of IgG antibodies to the Q fever bacteria.

Although recommended in most treatment guidelines, measuring antibodies to Q fever bacteria may not provide a good indication of disease activity, since many patients diagnosed with "possible chronic Q fever" have no evidence of chronic infection or complications. Nevertheless, they have persistent, high IgG antibody levels after the primary infection. Moreover, blood levels of IgG antibodies vary in individual patients, which can also be due to measurement errors and therefore does not always accurately reflect the course of the disease. Therefore, researchers from UMC Utrecht, Radboudumc and Jeroen Bosch Hospital investigated the predictive value of IgG antibody measurement in a study using data from the Dutch Chronic Q fever Database.

No relation with mortality

A total of 337 patients from both academic and peripheral hospitals treated for proven/suspected chronic Q fever were included in the analysis. Of these, 264 had been treated for at least 1 year, most with doxycycline plus hydroxychloroquine. Complications occurred in 190 (56 percent), death from chronic Q fever in 71 (21 percent), and therapy failure in 142 (42 percent) patients.

Alternative markers needed

Lead researcher at UMC Utrecht, Dr. Jan Jelrik Oosterheert, an internist-infectiologist at the Department of Infectious Diseases, concludes, "In the largest study conducted to date, we have shown that measuring antibodies to Q fever bacteria is not a reliable measure of mortality, complications or therapy failure." He and Professor of Outbreaks of Infectious Diseases Chantal Bleeker-Rovers of the Radboudumc state, "Therefore, we need alternative markers to properly follow patients in their disease process. Until such disease markers are developed and validated, the treatment of patients with chronic Q fever must be based on clinical symptoms, outcome of PCR tests and, for example, a PET-CT scan."

Chronic Q fever guidelines

After infection with Q fever bacteria, chronic Q fever develops in 1-5 percent of patients, often causing endocarditis (inflammation of the inner wall of the heart and heart valves) or infection of the vascular wall. Generally, long-term treatment with at least two antibiotics is indicated for patients with proven/probable chronic Q fever infection, typically for a duration of 18-24 months. The results of the present study nuance the current Dutch guidelines that recommend a follow-up of 5 years for serum IgG antibodies and to aim for a 4-fold reduction of these antibodies after discontinuation of antibiotics.

Radboudumc Q-Fever Expertise Center

In the Radboudumc Q fever Expertise Centre (in Dutch), patients with Q fever have been treated since 2008. The Radboud Q fever Expertise Centre collaborates with hospitals in the region. We also work closely with the GGD, the RIVM, Q-uestion, the Foundation for People with Q-Fever, Q-support and the Dutch Knowledge Centre for Chronic Fatigue (NKCV).

Publication in Clinical Microbiology and Infection

The prognostic value of serological titres for clinical outcomes during treatment and follow-up of patients with chronic Q fever - Buijs SB, Roeden SE van, Werkhoven CH van, Hoepelman AIM, Wever PC, Bleeker-Rovers CP, Oosterheert JJ. DOI: https://doi.org/10.1016/j.cmi.2021.03.016.

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