Orientia tsutsugamushiBacteremia 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-␥) 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-␣) and IL-1␤ concentrations. Regression analysis of DNA concentrations and cytokine levels identified a significant positive relationship for IL-10 (P < 0.0182) but not for IFN-␥, TNF-␣, and IL-1␤. 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.

Dissemination of Orientia tsutsugamushi and Inflammatory Responses in a Murine Model of Scrub Typhus

“…For qPCR-based quantification of O. tsutsugamushi , the majority of methods are based on the quantification of single copy genes that often yield high cycle threshold (Ct) values and low bacterial copy numbers, thus compromising statistical analyses [9], [20], [24], [25].…”

Significantly Higher Cytokine and Chemokine Levels in Patients with Japanese Spotted Fever than in Those with Tsutsugamushi Disease

“…We estimate that hypercytokinemia may contribute to the disease severity of rickettsiosis, including JSF. For instance, fulminant TD has been associated with hemophagocytic syndrome (10), and this syndrome may represent a hyperreaction of the immune system mediated by an overactivated cytokine network during the advanced stages of rickettsial infection (19,(26)(27)(28). We previously reported that a downregulation of these cytokines and chemokines is observed after the administration of tetracyclines, demonstrated a correlation between the severity of TD and the serum concentration of TNF-␣ in the acute phase of the disease, and showed that TNF-␣ levels are predictive of the severity of TD (18,19,29,30).…”

Unresolved Problems Related to Scrub Typhus: A Seriously Neglected Life-Threatening Disease

“…[87][88][89][90][91][92] However, mechanistic studies of protective or deleterious effects of these molecules have not been pursued. Indeed, the roles of CD4 and CD8 T lymphocytes, natural killer (NK) cells, NKT cells, dendritic cells, macrophages, and endothelial cells have not been evaluated in animal models with disseminated endothelial infection that appropriately represents scrub typhus (Table 4).…”