Long-term persistence of Coxiella burnetii after acute primary Q fever.
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.


OBJECTIVE
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).


METHODS
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 approximately 88% of Birmingham patients. No coxiella were isolated from PCR positive samples.


CONCLUSIONS
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.
Marmion
B P
BP
Q Fever Research Group, Infectious Diseases LAboratories, IMVS and Hanson Institute, Adelaide, South Australia. chris.nikolaou@imvs.sa.gov.au
Storm
P A
PA
Ayres
J G
JG
Semendric
L
L
Mathews
L
L
Winslow
W
W
Turra
M
M
Harris
R J
RJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001853:Bone Marrow / Q000382:microbiology; D002353:Carrier State / Q000276:immunology / Q000382:microbiology*; D002478:Cells, Cultured; D016997:Coxiella burnetii / Q000276:immunology / Q000302:isolation & purification*; D004269:DNA, Bacterial / Q000032:analysis; D005500:Follow-Up Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction / Q000379:methods; D011778:Q Fever / Q000382:microbiology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D004269:DNA, Bacterial