Orientia tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus.

Walsh, Douglas S.; Myint, Khin Saw Aye; Kantipong, Pacharee; Jongsakul, Krisada; Watt, George

doi:10.4269/ajtmh.2001.65.899

Cited by 35 publications

(15 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In experimental animals, O. tsutsugamushi infects peritoneal mesothelial cells [10], macrophages [11] and polymorphonuclear leukocytes [12]. In humans, O. tsutsugamushi has been detected in peripheral blood mononuclear cells (PBMCs) from patients with acute scrub typhus [13].…”

Section: Introductionmentioning

confidence: 99%

Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes: Relationship with Gene Expression in Patients with Scrub Typhus

et al. 2011

View full text Add to dashboard Cite

Orientia tsutsugamushi is the causal agent of scrub typhus, a public health problem in the Asia-Pacific region and a life-threatening disease. O. tsutsugamushi is an obligate intracellular bacterium that mainly infects endothelial cells. We demonstrated here that O. tsutsugamushi also replicated in monocytes isolated from healthy donors. In addition, O. tsutsugamushi altered the expression of more than 4,500 genes, as demonstrated by microarray analysis. The expression of type I interferon, interferon-stimulated genes and genes associated with the M1 polarization of macrophages was significantly upregulated. O. tsutsugamushi also induced the expression of apoptosis-related genes and promoted cell death in a small percentage of monocytes. Live organisms were indispensable to the type I interferon response and apoptosis and enhanced the expression of M1-associated cytokines. These data were related to the transcriptional changes detected in mononuclear cells isolated from patients with scrub typhus. Here, the microarray analyses revealed the upregulation of 613 genes, which included interferon-related genes, and some features of M1 polarization were observed in these patients, similar to what was observed in O. tsutsugamushi-stimulated monocytes in vitro. This is the first report demonstrating that monocytes are clearly polarized in vitro and ex vivo following exposure to O. tsutsugamushi. These results would improve our understanding of the pathogenesis of scrub typhus, during which interferon-mediated activation of monocytes and their subsequent polarization into an M1 phenotype appear critical. This study may give us a clue of new tools for the diagnosis of patients with scrub typhus.

show abstract

Section: Introductionmentioning

confidence: 99%

Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes: Relationship with Gene Expression in Patients with Scrub Typhus

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Azithromycin may be better suited than other macrolides for the treatment of scrub typhus. Azithromycin effectively penetrates human polymorphonuclear leukocytes and macrophages, which are target cells for O. tsutsugamushi, and its long tissue half-life of 2-4 days allows for a short course of therapy for infectious diseases that are caused by various intracellular pathogens [19,[32][33][34][35][36][37]. Moreover, the in vitro effectiveness of azithromycin against various strains of O. tsutsugamushi, irrespective of whether they are resistant or susceptible to doxycycline, has been documented [20].…”

Section: Discussionmentioning

confidence: 96%

A Comparative Trial of a Single Dose of Azithromycin versus Doxycycline for the Treatment of Mild Scrub Typhus

Kim

Yun

Shim

et al. 2004

Clinical Infectious Diseases

121

View full text Add to dashboard Cite

show abstract

“…In the early phase when O. tsutsugamushi multiplies at the bite site and in endothelium, shedding of organisms via the bloodstream therefore seems unlikely. In the later phase of the disease, however, the organism replicates in macrophages (14). Symptoms may be triggered mostly through immune cells in the skin and in local lymph nodes, rather than resulting from immediate systemic distribution of bacteria.…”

Section: Vol 47 2009mentioning

confidence: 99%

Orientia tsutsugamushiBacteremia and Cytokine Levels in Vietnamese Scrub Typhus Patients

Kramme

An²,

Khoa³

et al. 2009

J Clin Microbiol

View full text Add to dashboard Cite

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.

show abstract

Orientia tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus.

Cited by 35 publications

References 12 publications

Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes: Relationship with Gene Expression in Patients with Scrub Typhus

Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes: Relationship with Gene Expression in Patients with Scrub Typhus

A Comparative Trial of a Single Dose of Azithromycin versus Doxycycline for the Treatment of Mild Scrub Typhus

Orientia tsutsugamushiBacteremia and Cytokine Levels in Vietnamese Scrub Typhus Patients

Contact Info

Product

Resources

About