2007 ME/CFS Research Forum

ME/CFS RESEARCH FORUM: 26-27 March 2007
University of Adelaide
Convenor: Alison Hunter Memorial Foundation

Marmion B*, and Q fever Research Group, Adelaide South Australia.


Post Infection Fatigue Complex after Acute Q Fever

In 1996 the Adelaide Q fever Research Group (AQRG) described a severe, highly debilitating illness (Q fever Fatigue Syndrome=QFS), lasting many years, which followed 10-20% of laboratory- verified cases of acute primary Q fever. At about the same time the same sequelae were observed independently in a large sheep-associated outbreak in Birmingham UK. Since then the same phenomenon has been described in a goat--associated outbreak in Canada, in the military returning from Iraq and possibly in Prof. De Meirleir’s patient group in Belgium.

A questionnaire-based survey was administered to abattoir workers in Adelaide, who had proven clinical Q fever, or sub-clinical infection detected serologically, or who had been vaccinated against Q fever. A control group of non-exposed, sero-negative Telecom workers was also surveyed. This showed that the symptom complex of QFS was significantly more frequent in those who had clinically overt Q fever compared with the other three groups.

The symptom complex of QFS is monotonously stereotypic and closely similar to that of CFS. Symptomatically it could be interpreted as a persistent, downsized version of the cytokine-mediated acute phase reaction but without the fever and inflammatory markers, except in episodes of exacerbation following a presumptive re-exposure to the coxiella.

Subsequent investigations by the AQRG of QFS were:-- 1) comparisons of peripheral blood mononuclear cells from Australian QFS patients and controls to assay aberrant, dysregulated cytokine release patterns when stimulated in short term culture with Q fever and other antigens. 2) examination of bone marrow aspirates, thin needle liver biopsies and PBMC packs from Australian or Birmingham patients for evidence of infection by cell culture, animal inoculation and the presence of C burnetii genome by PCR amplification of various target sequences in its DNA. And 3) determination of HLA haplotypes and other immunogenetic gene polymorphisms in patients with QFS, Q fever endocarditis and those who had made an uncomplicated recovery from the original acute infection ("recovered").

The cytokine dysregulation studies showed that compared with controls, QFS patients had statistically significant increases in IL-6, variable increases in Interferon gamma and down regulation of IL-2.
The PCR studies detected coxiella genomic DNA in 65 to 88% of bone marrow samples of Q fever patients irrespective of whether they had QFS or not, although the QFS patients were significantly more frequently positive in the PBMC samples. The QFS and "recovered" groups had the same geometric antibody titres. Efforts to isolate the coxiella from PCR positive bone marrow, or PBMC samples have been negative so far although efforts continue with more sensitive systems. At present it appears that the PCR assays detect dead or replication-defective small cell variants of the coxiella but with intact cell structure protecting cell DNA and exhibiting the Phase 1 and 2 antigens of the organism. [Non-viable coxiellas have been detected in large numbers in Q fever endocarditis valves 15 or more years after initial infection]

The immunogenetic polymorphism studies showed, in the QFS group, a significantly higher prevalence of HLA DR B1*11types and allelic variation in a control sequence for interferong, compared with the "recovered" group and healthy control panels. Patterns in the Q fever endocarditis group differed from those in the other two groups.

A general hypothetical paradigm or model for a sector of the Chronic Fatigue Syndrome may be extrapolated from these patterns.

*Retired and Q fever Consultancy. Formerly, Chief Investigator, AQFRG and Visiting Professor, University of Adelaide and IMVS/Hanson Institute.


Alison Hunter Memorial Foundation
PO Box 6132 North Sydney 2059 Australia
Phone/Fax +61 2 9958 6285

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