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Journal of Clinical Microbiology, March 2009, p. 586-589, Vol. 47, No. 3
0095-1137/09/$08.00+0     doi:10.1128/JCM.00997-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Orientia tsutsugamushi Bacteremia and Cytokine Levels in Vietnamese Scrub Typhus Patients{triangledown}

Stefanie Kramme,1 Le Van An,2 Nguyen Dinh Khoa,2 Le Van Trin,2 Egbert Tannich,1 Jan Rybniker,1 Bernhard Fleischer,1 Christian Drosten,1 and Marcus Panning1*

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany,1 Hue Medical College, Hue, Vietnam2

Received 23 May 2008/ Returned for modification 13 October 2008/ Accepted 5 January 2009

Scrub typhus, caused by the intracellular bacterium Orientia tsutsugamushi, is a major cause of febrile illness in the Asia/Pacific region. Here, we implemented a novel real-time PCR and determined the relation of DNA target gene concentration with serum cytokine levels. The limit of detection of the novel real-time PCR was 1,062 DNA copies per ml of EDTA whole blood. Specificity was excellent as determined on a panel of blood- and skin-borne bacteria, including Rickettsia spp. as well as healthy Vietnamese blood donors. Bacterial DNA concentrations after 9 to 12 days from symptoms onset were significantly higher than in earlier or later periods (P < 0.05). Significantly higher concentrations of gamma interferon (IFN-{gamma}) and interleukin-10 (IL-10) occurred during the acute phase of disease (<10 days from onset) as opposed to the convalescent phase (P < 0.05). No significant differences were observed between the acute and the convalescent phases for tumor necrosis factor alpha (TNF-{alpha}) and IL-1β concentrations. Regression analysis of DNA concentrations and cytokine levels identified a significant positive relationship for IL-10 (P < 0.0182) but not for IFN-{gamma}, TNF-{alpha}, and IL-1β. In conclusion, proinflammatory cytokines and IL-10 were differentially related to human bacteremia. They may thus be induced by different constituents of O. tsutsugamushi. As a future prospect in a clinical diagnostic laboratory, quantitative real-time PCR may serve as a reliable tool to monitor therapy and to detect treatment failure.


* Corresponding author. Mailing address: Institute of Virology, University of Bonn Medical Centre, Sigmund Freud-Str. 25, 53127 Bonn, Germany. Phone: 49-228-287-16986. Fax: 49-228-287-19144. E-mail: panning{at}virology-bonn.de

{triangledown} Published ahead of print on 14 January 2009.


Journal of Clinical Microbiology, March 2009, p. 586-589, Vol. 47, No. 3
0095-1137/09/$08.00+0     doi:10.1128/JCM.00997-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.