Follow-up of 686 patients with acute Q fever and detection of chronic infection.

BACKGROUND: Recent outbreaks in the Netherlands allowed for laboratory follow-up of a large series of patients with acute Q fever and for evaluation of test algorithms to detect chronic Q fever, a condition with considerable morbidity and mortality. METHODS: For 686 patients with acute Q fever, IgG antibodies to Coxiella burnetii were determined using an immunofluorescence assay at 3, 6, and 12 months of follow-up. Polymerase chain reaction (PCR) was performed after 12 months and on earlier serum samples with an IgG phase I antibody titer ≥ 1:1024. RESULTS: In 43% of patients, the IgG phase II antibody titers remained high (≥ 1:1024) at 3, 6, and 12 months of follow-up. Three months after acute Q fever, 14% of the patients had an IgG phase I titer ≥ 1:1024, which became negative later in 81%. IgG phase I antibody titers were rarely higher than phase II titers. Eleven cases of chronic Q fever were identified on the basis of serological profile, PCR results, and clinical presentation. Six of these patients were known to have clinical risk factors at the time of acute Q fever. In a comparison of various serological algorithms, IgG phase I titer ≥ 1:1024 at 6 months had the most favorable sensitivity and positive predictive value for the detection of chronic Q fever. CONCLUSIONS: The wide variation of serological and PCR results during the follow-up of acute Q fever implies that the diagnosis of chronic Q fever, necessitating long-term antibiotic treatment, must be based primarily on clinical grounds. Different serological follow-up strategies are needed for patients with and without known risk factors for chronic Q fever.

Proximity to goat farms and Coxiella burnetii seroprevalence among pregnant women.

During 2007-2009, we tested serum samples from 2,004 pregnant women living in an area of high Q fever incidence in the Netherlands. Results confirmed that presence of antibodies against Coxiella burnetii is related to proximity to infected dairy goat farms. Pregnant women and patients with certain cardiovascular conditions should avoid these farms.

Antibodies against Coxiella burnetii and pregnancy outcome during the 2007-2008 Q fever outbreaks in The Netherlands.

BACKGROUND: Q fever has become a major public health problem in The Netherlands. Infection with Coxiella burnetii (Q fever) during pregnancy has resulted in adverse pregnancy outcome in the majority of reported cases. Therefore, we aimed to quantify this risk by examining the earliest periods corresponding to the epidemic in The Netherlands. METHODS: Serum samples that had been collected from the area of highest incidence by an existing national prenatal screening programme and data from the Netherlands Perinatal Registry (PRN) on diagnosis and outcome were used. We performed indirect immunofluorescence assay to detect the presence of IgM and IgG antibodies against C. burnetii in the samples. The serological results were analyzed to determine statistical association with recorded pregnancy outcome. RESULTS: Evaluation of serological results for 1174 women in the PRN indicated that the presence of IgM and IgG antibodies against phase II of C. burnetii was not significantly associated with preterm delivery, low birth weight, or several other outcome measures. CONCLUSION: The present population-based study showed no evidence of adverse pregnancy outcome among women who had antibodies to C. burnetii during early pregnancy.

Markers of infection in inpatients and outpatients with acute Q-fever.

BACKGROUND: Query-fever (Q-fever) is a zoonotic infection caused by the intracellular Gram-negative coccobacillus Coxiella burnetii. A large ongoing outbreak of Q-fever has been reported in the Netherlands. We studied various markers of infection in inpatients (hospitalised) and outpatients (treated by a general physician) with acute Q-fever in relation to disease severity. METHODS: Leukocyte counts, C-reactive protein (CRP) and procalcitonin (PCT) concentrations were measured in 25 inpatients and 40 outpatients upon presentation with acute Q-fever. Chest X-rays, if available, were analysed and confusion, urea, respiratory rate, blood pressure-age 65 (CURB-65) scores, indicating severity of pneumonia, were calculated. RESULTS: CRP was the only marker that significantly differentiated between inpatients and outpatients. It was increased in all patients from both groups. Leukocyte counts and PCT concentrations did not differ between inpatients and outpatients. Overall, only 13/65 patients had an increased leukocyte count and only 11/65 patients presented with PCT concentrations indicative of possible bacterial respiratory tract infection. Infiltrative changes on the chest X-ray were observed in the majority of patients. CURB-65 score was 0+/-1 (mean+/-SD). CONCLUSIONS: Acute Q-fever, a relatively mild pneumonia with low CURB-65 scores, specifically induces a response in CRP, while PCT concentrations and leukocytes are within the normal range or increased only marginally.

Evaluation of a diagnostic algorithm for acute Q fever in an outbreak setting.

In the peak of the 2009 Q fever outbreak in the Netherlands, we introduced a diagnostic algorithm for acute Q fever with an enzyme-linked immunosorbent assay for immunoglobulin M antibodies to Coxiella burnetii phase II antigens (MII screen) as an initial step. Subsequently, an immunofluorescence assay or PCR was performed depending on the MII screen outcome, date of onset of disease, and inpatient or outpatient setting. The impact of MII screen on the number of immunofluorescence assays performed and the contribution of PCR to diagnosis were retrospectively evaluated in 825 patients referred in a 17-day period. Acute Q fever was diagnosed in 256 patients. The introduction of MII screen reduced the number of immunofluorescence assays performed by more than 80%. In 103 patients, PCR analysis contributed to the diagnosis of acute Q fever. Q fever diagnostics were hampered by the fact that for a high number of patients the date of onset of disease was not provided and the requested follow-up serum samples were not received.