Marmion, B.Storm, P.Ayres, J.Semendric, L.Mathews, L.Winslow, W.Turra, M.Harris, R.2006-12-032006-12-032005QJM: an international journal of medicine, 2005; 98(1):7-201460-27251460-2393http://hdl.handle.net/2440/17156<h4>Background</h4>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.<h4>Aim</h4>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).<h4>Design</h4>Case follow-up study.<h4>Methods</h4>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.<h4>Results</h4>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 approximately 88% of Birmingham patients. No coxiella were isolated from PCR positive samples.<h4>Discussion</h4>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 patient's immunogenetic background to give higher levels of coxiella genomes in bone marrow and increased shedding into the peripheral blood. In Q fever endocarditis, late pregnancy, or during iatrogenic or other immunosuppression, the multiplication cycle is prolonged, and a potential source of live organisms.enLiverLeukocytes, MononuclearCells, CulturedBone MarrowAnimalsMice, KnockoutHumansMiceCoxiella burnetiiQ FeverDNA, BacterialAntibodies, BacterialAntigens, BacterialFollow-Up StudiesPolymerase Chain ReactionCarrier StateJournal article002005129710.1093/qjmed/hci0370002265174000022-s2.0-1244434192054438