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.

All specimens, including a recently excised heart valve from a Birmingham patient with late developing endocarditis, were infection negative in SCID mice. Dilutions of SCID mouse spleen and liver homogenates titrated in PCR assays were negative at dilutions attained by control mice inoculated with an endpoint dilution of a viable prototype strain of C. burnetii. Sections of the spleens from all specimens showed a complex of coxiella antigen-LPS by IFA. DISCUSSION/REVIEW: We advance a concept of long-term persistence of a non-infective, non-biodegraded complex of coxiella cell components with its antigens and specific LPS [so called Immunomodulatory complex (IMC)] associated with traces of genomic DNA that signalled its presence in our earlier studies. The IMC's survival in patients for at least 12 years, and in one patient for 70 years implies a capacity for serial passage in macrophages with effective down-regulation of their biodegrading functions. The review assesses the compatibility of the IMC concept in relation to cogent literature on C. burnetii interactions with macrophage and cell-mediated immunity. Some remaining gaps in our knowledge of the organ sites and duration of carriage of viable coxiellas after initial infection are also identified.

The study identifies a non-infective complex of C.b. antigens able to survive in the host and provoke aberrant humoral and cell medicated immunity responses - a possible pathogenic link between initial infection and a subsequent long-term post Q fever fatigue syndrome.