Background: Long-term persistence of C. burnetii in infected animals was established in the 1950s and 60s, but the implications for human Q fever are not fully explored.
Aim: To compare the prevalence of markers of infection in a cohort of Q fever patients in Australia (up to 5 years after infection) with those in the 1989 Birmingham cohort (12 years after infection).
Design: Case follow-up study.
Methods: C. burnetii was tested for by: (i) antibodies to Phase 1 and 2 antigens in the three immunoglobulin classes; (ii) detection of DNA in bone marrow and peripheral blood mononuclear cells by PCR assays directed against several different targets in the genome; and (iii) attempts to isolate coxiellas in cell culture or mice from PCR-positive samples. Amplicon specificity was verified by fluorometric probing and by sequencing. Cross-contamination was excluded by extensive use of non-template controls, and in particular by the use of certain IS1111a target sequences.
Results: Irrespective of clinical state, both groups remained seropositive, principally exhibiting-medium levels of IgG antibody against C burnetii Phase 2 antigen. C burnetii genomic DNA was detected by PCR in 65% of bone marrow aspirates from Australian patients and similar to88% of Birmingham patients. No coxiella were isolated from PCR positive samples.
Discussion: We propose a provisional model for persistence. In Q fever without sequelae, the process is largely confined to the bone marrow. In Q fever fatigue syndrome (QFS), it is modulated by the patients immunogenetic back-round to give higher levels of coxiella genomes in bone marrow and increased shedding into the peripheral blood. In Q fever endocarditis, late pregnancy, of during iatrogenic or other immunosuppression, the multiplication cycle is prolonged, and a potential source of live organisms.