title: Microbiological challenges in the diagnosis of chronic Q fever.
abstract: Diagnosis of chronic Q fever is difficult. PCR and culture lack sensitivity; hence, diagnosis relies mainly on serologic tests using an immunofluorescence assay (IFA). Optimal phase I IgG cutoff titers are debated but are estimated to be between 1:800 and 1:1,600. In patients with proven, probable, or possible chronic Q fever, we studied phase I IgG antibody titers at the time of positive blood PCR, at diagnosis, and at peak levels during chronic Q fever. We evaluated 200 patients, of whom 93 (46.5%) had proven, 51 (25.5%) had probable, and 56 (28.0%) had possible chronic Q fever. Sixty-five percent of proven cases had positive Coxiella burnetii PCR results for blood, which was associated with high phase I IgG. Median phase I IgG titers at diagnosis and peak titers in patients with proven chronic Q fever were significantly higher than those for patients with probable and possible chronic Q fever. The positive predictive values for proven chronic Q fever, compared to possible chronic Q fever, at titers 1:1,024, 1:2,048, 1:4,096, and ≥1:8,192 were 62.2%, 66.7%, 76.5%, and ≥86.2%, respectively. However, sensitivity dropped to <60% when cutoff titers of ≥1:8,192 were used. Although our study demonstrated a strong association between high phase I IgG titers and proven chronic Q fever, increasing the current diagnostic phase I IgG cutoff to >1:1,024 is not recommended due to increased false-negative findings (sensitivity < 60%) and the high morbidity and mortality of untreated chronic Q fever. Our study emphasizes that serologic results are not diagnostic on their own but should always be interpreted in combination with clinical parameters.
authors.affiliation: Division of Medicine, Dept. of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands. l.m.kampschreur@umcutrecht.nl
authors.forename: Linda M
authors.initials: LM
authors.lastname: Kampschreur
authors.forename: Jan Jelrik
authors.initials: JJ
authors.lastname: Oosterheert
authors.forename: Annemarie M C
authors.initials: AM
authors.lastname: Koop
authors.forename: Marjolijn C A
authors.initials: MC
authors.lastname: Wegdam-Blans
authors.forename: Corine E
authors.initials: CE
authors.lastname: Delsing
authors.forename: Chantal P
authors.initials: CP
authors.lastname: Bleeker-Rovers
authors.forename: Monique G L
authors.initials: MG
authors.lastname: De Jager-Leclercq
authors.forename: Cornelis A R
authors.initials: CA
authors.lastname: Groot
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
authors.forename: Marrigje H
authors.initials: MH
authors.lastname: Nabuurs-Franssen
authors.forename: Nicole H M
authors.initials: NH
authors.lastname: Renders
authors.forename: Marjo E
authors.initials: ME
authors.lastname: van Kasteren
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Soethoudt
authors.forename: Sybrandus N
authors.initials: SN
authors.lastname: Blank
authors.forename: Marjolijn J H
authors.initials: MJ
authors.lastname: Pronk
authors.forename: Rolf H H
authors.initials: RH
authors.lastname: Groenwold
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Peter C
authors.initials: PC
authors.lastname: Wever
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood*; D019411:Clinical Laboratory Techniques / Q000379:methods*; D016997:Coxiella burnetii / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011778:Q Fever / Q000175:diagnosis*; D012680:Sensitivity and Specificity
chemical_list: D000907:Antibodies, Bacterial; D004269:DNA, Bacterial; D007074:Immunoglobulin G