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Re: Rickettsial antibody levels and mitochondrial gene expression in CFS patients

Dear Editor,

Kaushik et al.[1] have demonstrated significantly different gene expression in a small sample of patients with chronic fatigue syndrome. They suggest these observations are consistent with a complex pathogenesis involving T cell activation and abnormalities of neuronal and mitochondrial function, possibly as a result of virus infection or organophosphate exposures.

We suggest that chronic ricketssial infections would be an equally plausible hypothesis, consistent with Kaushik's observations, and worthy of further study. Like viruses rickettsiae are obligate intracellular parasites. Jadin[2] observed in South Africa that, for 500 patients diagnosed with CFS, ME or depression, 80% tested positive to abnormally high levels of ricketssial antibodies using a multiple microagglutination test for antibodies to R Prowazeki, R Mooseri, R Conori, and Coxiella Burnetti ( itself a neo rickettsia).[3]

In the clinical practice of one of the authors (Kemp) all chronically unwell patients, in whom fatigue and/or fibromyalgia are significant, are routinely tested for rickettsia using IgG serology. Over a recent three year period 67% of 750 such patients returned positive serology to at least one of the four rickettsial groups tested, with a titration level of 1/128 or greater considered positive. This data will be submitted for publication at a later time.

Of the seropositive patients only a very small percentage test positive to rickettsiae via real time PCR testing. Moreover very few can recall any incidents in their medical history which would be consistent with an acute rickettsial infection. Most respond significantly to extended antibiotic treatment, mainly using rotating tetracyclines, as described by Jadin (op cit).

While rickettsiae do produce some energy from independent metabolism[4], and can themselves produce small amounts of protein, the energy required for cell division must come from the host cell's mitachondria and the protein sequences from the host cytoplasm. Krausnik's observations of significant perturbation of mitochondrial gene expression might therefore be consistent with chronic rickettsial parasitic infections.

Unlike most viruses ricketsiae can live for quite extended periods in extracellular fluid. Isolated (i.e. non parasitising) rickettsiae can accumulate lysine and lyse erythrocytes, demonstrating their capacity to operate an electron transport system.[5] Their survival in extracellular fluid might contribute to chronic infection and be consistent with Chronic Fatigue patient histories.

Writing in Nature in 1998 Anderson et al.[6] have demonstrated through phylogenetic analyses that R. prowazekii is genetically very closely related to mitochondria. At the time of writing they observed that no other bacteria was as closely related to mitachondria.

While undoubtedly speculative, it is tempting to think that a parasitic bacteria whose replication is absolutely dependent upon the host cell's mitachondria and whose reproductive DNA formation requirements closely match those of the host's mitachondria will be engaged in competition with both the host cell's own energy and own reproductive needs. If this competition resulted in lower levels of mitochondrial capability then a rickettsial etiology for CFS might also explain the functional fatigue seen as the very essence of chronic fatigue syndrome.

G C M Kemp MB BS(Melb) FRACGP, FACNEM
Burke Road Medical Centre
681 Burke Road
Camberwell 3134 Australia

R F Townsend PhD (UNSW) BE (Melb) BBus(Mitchell)
Honorary Research Fellow, Department of Biomolecular Engineering
University of Melbourne,
Parkville 3004 Australia

References

1. N Kaushik, D Fear, S C M Richards, C R McDermott, E F Nuwaysir, P Kellam, T JHarrison, R J Wilkinson, D A J Tyrrell, S T Holgate and J R Kerr Gene expression in peripheral blood mononuclearcells from patients with chronic fatigue syndrome J. Clin. Pathol. 2005;58;826-832

2. C L Jadin, Common Clinical Windows on CFS and Rickettsial Diseases. Journal of Chronic Fatigue Syndrome, 6 no 3 133-145 2000

3. Fiset, P., R. A. Ormsbee, R. Silberman, M. Peacock, and S. H. Spielman.1969. A microagglutination technique for detection and measurement ofrickettsial antibodies. Acta Virol. 13:60–66 and also Kazar, J., R. Brezina, S. Schramek, A. Palanova, and B. Tvrda. 1981 Suitability of the microagglutination test for detection of post-infection and post- vaccination Q fever antibodies in human sera. Acta Virol. 25:235–240.

4. Rickettsial surival in synthetic in vitro solutions have demonstrated that Rickettsial respiration is possible from a wide range of amino acids and sugars,

5. Smith, D. K., and H. H. Winkler. 1977. Characterization of a lysine-specific active transport system in Rickettsia prowazekii.J. Bacteriol. 129:1349-1355.

6. The genome sequence of Rickettsia prowazekii and the origin of mitochondria Siv G. E. Andersson, Alireza Zomorodipour, Jan O. Andersson, Thomas Sicheritz-Ponte ,U. Cecilia M. Alsmark, Raf M. Podowski, A. Kristina, Ann-Soe Eriksson, Herbert H. Winkler Nature vol 396 no 12 November 1998.