title: Orientia tsutsugamushi bacteremia and cytokine levels in Vietnamese scrub typhus patients.
abstract: 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-1beta 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-1beta. 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.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kramme
authors.forename: Le Van
authors.initials: le V
authors.lastname: An
authors.forename: Nguyen Dinh
authors.initials: ND
authors.lastname: Khoa
authors.forename: Le Van
authors.initials: le V
authors.lastname: Trin
authors.forename: Egbert
authors.initials: E
authors.lastname: Tannich
authors.forename: Jan
authors.initials: J
authors.lastname: Rybniker
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleischer
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
authors.forename: Marcus
authors.initials: M
authors.lastname: Panning
mesh_terms: D016470:Bacteremia / Q000382:microbiology*; D016207:Cytokines / Q000097:blood*; D004269:DNA, Bacterial / Q000097:blood; D006801:Humans; D012285:Orientia tsutsugamushi / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction / Q000379:methods*; D012612:Scrub Typhus / Q000276:immunology* / Q000382:microbiology*; D012680:Sensitivity and Specificity; D014744:Vietnam
chemical_list: D016207:Cytokines; D004269:DNA, Bacterial