Long-term follow-up of acute Q fever patients after a large epidemic

Abstract

Between 2007 and 2009, one of the largest Q fever epidemics documented worldwide occurred in the Netherlands. This epidemic originated from dairy goat farms and resulted in over 3,500 notified human acute Q fever cases. After an episode of acute Q fever, the causative bacterium Coxiella burnetii may persist intracellularly, causing progression to chronic disease in approximately 2% of patients with confirmed acute Q fever. Chronic Q fever mainly presents as endocarditis or vascular infections with a high morbidity and mortality. Early detection and prompt treatment improve the prognosis of patients with chronic Q fever. The established way to detect chronic Q fever is to provide follow-up and check antibody levels of all acute Q-fever patients, but there is no consensus on its frequency and duration. The Q fever epidemic in the Netherlands allowed for long-term follow-up of a large cohort of acute Q-fever patients and validation of current follow-up strategies. More than 1,900 patients diagnosed at the Jeroen Bosch Hospital (’s-Hertogenbosch) with follow-up checks available in the first year after the acute episode were invited to have a blood sample taken approximately four years after the acute infection. The antibody levels were determined for 1,289 participants. Patients suspected for chronic Q fever were referred for further clinical examinations. Overall, 4.5% of the 1,289 participants had an antibody profile suggesting chronic Q feverduring the four years. The majority (89.7%) had already been identified within the first year after the acute episode. Based on these results, a single follow-up check twelve months after diagnosis is recommended for all the acute Q fever patients that have no risk factors for chronic Q fever (heart valve/vascular disease or prosthesis). Additional serological and clinical follow-up is recommended for patients with IgG phase I titres ≥1:512. Dutch Laboratories for Medical Microbiology implemented their own follow-up strategies. Large differences were found in follow-up rates within 15 months after diagnosis when comparing a laboratory that provided an active follow-up service by approaching patients directly and two laboratories that only tested on requests of physicians (95% versus 25% follow-up rate, respectively; odds ratio 54, 95% confidence interval 43−67). A study among 183 hospitalized Dutch acute Q fever patients showed that they mostly presented with fever and pneumonia. Hospitalized acute Q fever pneumonia patients were younger, had less co-morbidity, and lower pneumonia severity scores than hospitalized patients with another community-acquired pneumonia. PCR testing is a valuable tool in diagnosing acute Q fever in outbreak situations when the symptom onset is less than 15 days earlier. Patients who later developed serologic profiles indicative of chronic Q fever infection (IgG phase I ≥1:1,024) had significantly higher C. burnetii DNA loads during the acute phase than patients who did not develop such a serologic profile. When the antibody response develops, serology becomes the most important diagnostic tool. Immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and complement fixation test (CFT) perform equally well in diagnosing acute Q fever but two serum samples are needed for the definitive laboratory diagnosis.