Genotyping of Orientia tsutsugamushi from humans with scrub typhus, Laos.
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ABSTRACT:
SUBMITTER: Parola P
PROVIDER: S-EPMC2603112 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To verify the value of eschars for the diagnosis of scrub typhus and to characterize genotypes of Orientia tsutsugamushi in patients, we examined eschars and blood specimens of 7 patients from Shandong Province, People's Republic of China, for O. tsutsugamushi by polymerase chain reaction targeting the Sta56 gene. All 7 eschars and acute-phase blood samples were positive, while no specific DNA amplicons were obtained from the 7 convalescent-phase blood samples collected after antimicrobial drug therapy. The findings indicate that patients' eschars can be used for detection and genetic characterization of O. tsutsugamushi during the convalescent phase.
| S-EPMC3375733 | biostudies-literature
Project description:In a recent case of scrub typhus in Australia, Orientia tsutsugamushi isolated from the patient's blood was tested by sequence analysis of the 16S rDNA gene. The sequence showed a strain of O. tsutsugamushi that was quite different from the classic Karp, Kato, and Gilliam strains. The new strain has been designated Litchfield.
| S-EPMC2640248 | biostudies-other
Project description:BackgroundScrub typhus, a bacterial infection caused by Orientia tsutsugamushi, is increasingly recognized as an important cause of fever in Asia, with an estimated one million infections occurring each year. Limited access to health care and the disease's non-specific symptoms mean that many patients are undiagnosed and untreated, but the mortality from untreated scrub typhus is unknown. This review systematically summarizes the literature on the untreated mortality from scrub typhus and disease outcomes.Methodology/principal findingsA literature search was performed to identify patient series containing untreated patients. Patients were included if they were symptomatic and had a clinical or laboratory diagnosis of scrub typhus and excluded if they were treated with antibiotics. The primary outcome was mortality from untreated scrub typhus and secondary outcomes were total days of fever, clinical symptoms, and laboratory results. A total of 76 studies containing 89 patient series and 19,644 patients were included in the final analysis. The median mortality of all patient series was 6.0% with a wide range (min-max) of 0-70%. Many studies used clinical diagnosis alone and had incomplete data on secondary outcomes. Mortality varied by location and increased with age and in patients with myocarditis, delirium, pneumonitis, or signs of hemorrhage, but not according to sex or the presence of an eschar or meningitis. Duration of fever was shown to be long (median 14.4 days Range (9-19)).ConclusionsResults show that the untreated mortality from scrub typhus appears lower than previously reported estimates. More data are required to clarify mortality according to location and host factors, clinical syndromes including myocarditis and central nervous system disease, and in vulnerable mother-child populations. Increased surveillance and improved access to diagnostic tests are required to accurately estimate the untreated mortality of scrub typhus. This information would facilitate reliable quantification of DALYs and guide empirical treatment strategies.
| S-EPMC4537241 | biostudies-literature
Project description:Scrub typhus is a vector-borne, acute febrile illness caused by Orientia tsutsugamushi. Scrub typhus continues to be an important but neglected tropical disease in Nepal. Information on this pathogen in Nepal is limited to serological surveys with little information available on molecular methods to detect O. tsutsugamushi. Limited information exists on the genetic diversity of this pathogen. A total of 282 blood samples were obtained from patients with suspected scrub typhus from central Nepal and 84 (30%) were positive for O. tsutsugamushi by 16S rRNA qPCR. Positive samples were further subjected to 56 kDa and 47 kDa molecular typing and molecularly compared to other O. tsutsugamushi strains. Phylogenetic analysis revealed that Nepalese O. tsutsugamushi strains largely cluster together and cluster away from other O. tsutsugamushi strains from Asia and elsewhere. One exception was the sample of Nepal_1, with its partial 56 kDa sequence clustering more closely with non-Nepalese O. tsutsugamushi 56 kDa sequences, potentially indicating that homologous recombination may influence the genetic diversity of strains in this region. Knowledge on the circulating strains in Nepal is important to the development of diagnostic tests and vaccines to support public health measures to control scrub typhus in this country.
| S-EPMC8066985 | biostudies-literature
Project description:Scrub typhus, caused by antigenically disparate isolates of Orientia tsutsugamushi, is a widely distributed mite-borne human disease in the Asia Pacific region. Information regarding the heterogeneity of the immunodominant 56-kDa type-specific antigen (TSA) gene is crucial for the design and evaluation of scrub typhus-specific diagnostic assays and vaccines. Using indirect immunofluorescence assays (IFA) and PCR assays, O. tsutsugamushi was detected samples from rodents and patients with fever of unknown origin obtained from six provinces of Thailand during 2004 to 2007. Sequences were determined for a fragment of the 56-kDa TSA gene, and the relationship between these sequences and those previously determined were assessed. The phylogenetic analyses of partial 56-kDa TSA gene sequences demonstrated wide diversity and distribution of O. tsutsugamushi genotypes in Thailand. Furthermore, the genetic diversity grouped the scrub typhus agents into two commonly and five infrequently found genotypes within six provinces of Thailand. The two most commonly found genotypes of O. tsutsugamushi described in this study do not associate with the prototype strains that are widely used for the design and evaluation of diagnostic assays and vaccine candidates. Thus, these new genotypes should be considered for future scrub typhus assay and vaccine development.
| S-EPMC3147819 | biostudies-literature
Project description:Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, a bacterium that mainly infects endothelial cells in vitro and in vivo. Evidence suggests that the interaction of O. tsutsugamushi with myeloid cells may play a pivotal role in O. tsutsugamushi infection. We showed here that O. tsutsugamushi intensively replicated within human monocyte-derived macrophages. Bacterial organisms stimulated the expression of a large panel of genes including type I interferon, interferon-stimulated, inflammatory, apoptosis-related genes and induced an M1-type gene response in macrophages. This transcriptional signature was accompanied by functional consequences such as the release of inflammatory cytokines such as Tumor Necrosis Factor and interleukin-gamma. Live O. tsutsugamushi organisms were necessary for type I interferon response and, to a lesser degree, to inflammatory response. As interferon-gamma is known to elicit M1 polarization, we assessed the effect of interferon-gamma on O. tsutsugamushi fate in macrophages. Exogenous interferon-gamma partly inhibited O. tsutsugamushi replication within macrophages. Our results suggest that the inflammatory response induced by O. tsutsugamushi may account for the local and systemic inflammation observed in scrub typhus and that interferon-gamma may be useful as an adjuvant treatment of patients with scrub typhus.
2013-01-29 | GSE38194 | GEO
Project description:BackgroundScrub typhus, a febrile illness of substantial incidence and mortality, is caused by infection with the obligately intracellular bacterium Orientia tsutsugamushi. It is estimated that there are more than one million cases annually transmitted by the parasitic larval stage of trombiculid mites in the Asia-Pacific region. The antigenic and genetic diversity of the multiple strains of O. tsutsugamushi hinders the advancement of laboratory diagnosis, development of long-lasting vaccine-induced protection, and interpretation of clinical infection. Despite the life-threatening severity of the illness in hundreds of thousands of cases annually, 85-93% of patients survive, often without anti-rickettsial treatment. To more completely understand the disease caused by Orientia infection, animal models which closely correlate with the clinical manifestations, target cells, organ involvement, and histopathologic lesions of human cases of scrub typhus should be employed. Previously, our laboratory has extensively characterized two relevant C57BL/6 mouse models using O. tsutsugamushi Karp strain: a route-specific intradermal model of infection and persistence and a hematogenously disseminated dose-dependent lethal model.Principal findingsTo complement the lethal model, here we illustrate a sublethal model in the same mouse strain using the O. tsutsugamushi Gilliam strain, which resulted in dose-dependent severity of illness, weight loss, and systemic dissemination to endothelial cells of the microcirculation and mononuclear phagocytic cells. Histopathologic lesions included expansion of the pulmonary interstitium by inflammatory cell infiltrates and multifocal hepatic lesions with mononuclear cellular infiltrates, renal interstitial lymphohistiocytic inflammation, mild meningoencephalitis, and characteristic typhus nodules.SignificanceThese models parallel characteristics of human cases of scrub typhus, and will be used in concert to understand differences in severity which lead to lethality or host control of the infection and to address the explanation for short duration of heterologous immunity in Orientia infection.
| S-EPMC5362142 | biostudies-literature
Project description:Orientia tsutsugamushi causes scrub typhus and is a rural zoonosis endemic in the Asia Pacific region. This is the first report of O. tsutsugamushi TA716-like strain in a human in Thailand. The patient was in the 1st trimester of pregnancy when she developed scrub typhus. The O. tsutsugamushi strain TA716 was detected from her admission blood sample, and the pregnancy ended in spontaneous abortion. The effects of scrub typhus in pregnant women and the pregnancy outcome are sparsely documented in the published medical literature. Improved clinical recognition and laboratory diagnosis will be essential to better define the morbidity caused by this zoonosis especially in pregnancy.
| S-EPMC2924790 | biostudies-literature
Project description:BackgroundScrub typhus is an acute febrile disease caused by Orientia tsutsugamushi infection. Recently, the rapid increase of scrub typhus incidence in several countries within the endemic region has become a serious public health issue. Despite the wide range of preventative approaches that have been attempted in the past 70 years, all have failed to develop an effective prophylactic vaccine. Currently, the selection of the proper antigens is one of the critical barriers to generating cross-protective immunity against antigenically-variable strains of O. tsutsugamushi.Methodology/principal findingsWe examined the potential role of ScaA protein, an autotransporter protein of O. tsutsugamushi, in bacterial pathogenesis and evaluated the protective attributes of ScaA immunization in lethal O. tsutsugamushi infection in mice. Our findings demonstrate that ScaA functions as a bacterial adhesion factor, and anti-ScaA antibody significantly neutralizes bacterial infection of host cells. In addition, immunization with ScaA not only provides protective immunity against lethal challenges with the homologous strain, but also confers significant protection against heterologous strains when combined with TSA56, a major outer membrane protein of O. tsutsugamushi.Conclusions/significanceImmunization of ScaA proteins provides protective immunity in mice when challenged with the homologous strain and significantly enhanced protective immunity against infection with heterologous strains. To our knowledge, this is the most promising result of scrub typhus vaccination trials against infection of heterologous strains in mouse models thus far.
| S-EPMC4359152 | biostudies-literature
Project description:Central aspects in the pathogenesis of scrub typhus, an infection caused by Orientia (O.) tsutsugamushi, have remained obscure. Its organ and cellular tropism are poorly understood. The purpose of this study was to analyze the kinetics of bacterial dissemination and associated inflammatory responses in infected tissues in an experimental scrub typhus mouse model, following infection with the human pathogenic strain Karp. We provide a thorough analysis of O. tsutsugamushi infection in inbred Balb/c mice using footpad inoculation, which is close to the natural way of infection. By a novel, highly sensitive qPCR targeting the multi copy traD genes, we quantitatively monitored the spread of O. tsutsugamushi Karp from the skin inoculation site via the regional lymph node to the internal target organs. The highest bacterial loads were measured in the lung. Using confocal imaging, we also detected O. tsutsugamushi at the single cell level in the lung and found a predominant macrophage rather than endothelial localization. Immunohistochemical analysis of infiltrates in lung and brain revealed differently composed lesions with specific localizations: iNOS-expressing macrophages were frequent in infiltrative parenchymal noduli, but uncommon in perivascular lesions within these organs. Quantitative analysis of the macrophage response by immunohistochemistry in liver, heart, lung and brain demonstrated an early onset of macrophage activation in the liver. Serum levels of interferon (IFN)-? were increased during the acute infection, and we showed that IFN-? contributed to iNOS-dependent bacterial growth control. Our data show that upon inoculation to the skin, O. tsutsugamushi spreads systemically to a large number of organs and gives rise to organ-specific inflammation patterns. The findings suggest an essential role for the lung in the pathogenesis of scrub typhus. The model will allow detailed studies on host-pathogen interaction and provide further insight into the pathogenesis of O. tsutsugamushi infection.
| S-EPMC4133189 | biostudies-literature