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Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen.

BACKGROUND: Zinc oxide nanoparticle (ZNP) has been applied in various biomedical fields. Here, we investigated the usage of ZNP as an antigen carrier for vaccine development by combining a high affinity peptide to ZNP. RESULTS: A novel zinc oxide-binding peptide (ZBP), FPYPGGDA, with high affinity to ZNP (K a  = 2.26 × 106 M-1) was isolated from a random peptide library and fused with a bacterial antigen, ScaA of Orientia tsutsugamushi, the causative agent of scrub typhus. The ZNP/ZBP-ScaA complex was efficiently phagocytosed by a dendritic cell line, DC2.4, in vitro and significantly enhance…

Field assessment of Orientia tsutsugamushi infection in small mammals and its association with the occurrence of human scrub typhus in Taiwan.

We conducted an extensive study in Taiwan of Orientia tsutsugamushi (OT) infection in small wild mammals. Field trapping was carried out at six districts in eastern and western Taiwan as well as various offshore islands during the period 2006-2010. A total of 1061 specimens representing 11 rodent species were captured. The presence of OT infection was assessed by indirect immunofluorescence assay and polymerase chain reaction assays of 56-kDa type-specific antigen gene. The chigger infestation rate among the animals was 35% (371/1061). Among these, OT was detected in 64% (238/371) of the chigg…

Orientia tsutsugamushi stimulates an original gene expression program in monocytes: relationship with gene expression in patients with scrub typhus.

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 significant…

Сопоставление экспресс-диагностического теста и микроиммунофлюоресценции для обнаружения антитела в организме пациентов с скрубами тифа в Китае.

ЦЕЛЬ: Оценить обнаружение антител IgM и IgG на основе экспресс-диагностического теста (RDT) и микроиммунофлюоресценции (MIFA). МЕТОДЫ: RDT с использованием смеси рекомбинантных протеинов 56 кДа из О. цуцугамуши и МИФА были выполнены 20 пациентов из Фуцзян и 13 пациентов из провинции Юньнань, а также 82 образца серы от здоровых фермеров в провинции Анхуй и городе Пекин в 2009 году. Сопоставление результатов анализа RDT и MIFA проводилось с использованием испытания X(2), а уровень P <0,05 был признан значимым. Результаты: Из этих 82 обычных образцов сера специфичность RDT была 100% для ИгМ и IgG

Совпадение в аннотации оригинала
OBJECTIVE: To evaluate the detection of IgM and IgG antibodies to Orientia tsutsugamushi (O. tsutsugamushi) by rapid diagnostic test (RDT) and microimmunofluorescence assay (mIFA). METHODS: RDT using a mixture of recombinant 56-kDa proteins of O. tsutsugamushi and mIFA assay were performed on 20 patients from Fujian and 13 patients from Yunnan Province, and…

Antigenic drift of Orientia tsutsugamushi in South Korea as identified by the sequence analysis of a 56-kDa protein-encoding gene.

This study was performed to determine the nationwide antigenic diversity of Orientia tsutsugamushi in South Korea. Sequence analysis was performed around variable domains I and II of a 56-kDa protein-encoding gene. We used eschar to overcome the disadvantages of conventional serotyping. The serological passive hemagglutination assay (PHA) was assessed based on the genotyping results. We analyzed 153 isolates from scrub typhus patients in major endemic areas and found that Boryong was the major strain (68.6%). New strains were also identified: Taguchi (19.6%), Kanda/Kawasaki (9.2%), and UAP7 (1…

Follow-up analysis on the epidemic strains of Orientia tsutsugamushi in the first outbreak of scrub typhus in Henan Province, China.

To obtain knowledge of the genetic characteristics and types of the epidemic strains of Orientia tsutsugamushi in the first outbreak of scrub typhus in Henan Province, genus and type-specific primers were employed to amplify a fragment of the gene of 56 kDa protein. Serotyping demonstrated that, of the 19 patients [15 patients in recovery phase (10-40 days) and 4 of patients in acute phase (1-7 days)], 4 were infected with Gilliam type, 8 with Kato type, 6 with Karp type, and 1 with an unknown type. Successful genotyping was obtained for only 3 patients, indicating that 2 were infected with Ka…

Ectoparasite diversity and Orientia tsutsugamushi infection in rodent hosts from scrub typhus-endemic areas of the Western Himalayas, India.

Scrub typhus has re-emerged as an important public health concern in Himachal Pradesh, India, and is caused by Orientia tsutsugamushi. Effective control efforts are limited by outdated data on ectoparasite vectors and infection rates among reservoir hosts in this endemic region of the Western Himalayas. We conducted a comprehensive field study across eight districts of Himachal Pradesh to examine ectoparasite diversity associated with rodents and shrews in an area endemic for scrub typhus. Small mammals such as rodents and shrews were trapped, and their ectoparasites were collected and morphol…

Molecular Epidemiology and Genetic Diversity of Orientia tsutsugamushi From Patients and Small Mammals in Xiangyun County, Yunnan Province, China.

INTRODUCTION: Scrub typhus, also known as Tsutsugamushi disease (TD), is an acute febrile illness that poses a significant public health threat to nearly one billion people in the Asia-Pacific region. The disease is caused by Orientia tsutsugamushi (OT) and is primarily transmitted through the bite of chigger mite larvae. Due to its nonspecific clinical manifestations, early diagnosis is challenging, often leading to misdiagnosis or untreated cases. Yunnan Province, located on China's border, reports the highest annual incidence of scrub typhus, highlighting the need to better understand OT in…

Molecular Detection of Multiple Genotypes of Orientia tsutsugamushi Causing Scrub Typhus in Febrile Patients from Theni District, South India.

Scrub typhus (St) is a re-emerging mite-transmitted public health problem in Southeast Asia with escalating case incidences in the endemic areas. Though, more than 40 genotypes of the causative agent Orientia tsutsugamushi (Ot) have been documented, the information on the circulating genotypes in India is scanty. A hospital-based retrospective screening was undertaken to map the circulating molecular subtypes of the etiological agent in serologically confirmed scrub typhus (St) human cases, by targeting the GroEL gene of O. tsutsugamushi using the nested polymerase chain reaction method. Nine …

Outer Membrane Protein A Conservation among Orientia tsutsugamushi Isolates Suggests Its Potential as a Protective Antigen and Diagnostic Target.

Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially-available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very si…

Diagnostic accuracy of a loop-mediated isothermal PCR assay for detection of Orientia tsutsugamushi during acute Scrub Typhus infection.

BACKGROUND: There is an urgent need to develop rapid and accurate point-of-care (POC) technologies for acute scrub typhus diagnosis in low-resource, primary health care settings to guide clinical therapy. METHODOLOGY/PRINCIPAL FINDINGS: In this study we present the clinical evaluation of loop-mediated isothermal PCR assay (LAMP) in the context of a prospective fever study, including 161 patients from scrub typhus-endemic Chiang Rai, northern Thailand. A robust reference comparator set comprising following 'scrub typhus infection criteria' (STIC) was used: a) positive cell culture isolate and/

Characterization of Orientia tsutsugamushi strains isolated in Shandong Province, China by immunofluorescence and restriction fragment length polymorphism (RFLP) analyses.

In order to identify the characteristics of the Sta56 gene of the 23 isolates of Orientia (O.) tsutsugamushi isolated in Shandong Province, indirect immunofluorescence assay (IFA) was used to identify the gene type of 23 strains O. tsutsugamushi isolated from scrub typhus patients, chigger mites, and rodents. Restriction fragment length polymorphism (RFLP) analysis was also used to analyze the restriction profiles of the Sta56 gene PCR amplification products of the 23 isolated strains of the O. tsutsugamushi; the results were compared with those acquired by nested PCR. By IFA, 21 of the 23 iso…

Antibodies to Orientia tsutsugamushi, Rickettsia typhi and spotted fever group rickettsiae among febrile patients in rural areas of Malaysia.

A serosurvey was conducted in 1995-97 among 1596 febrile patients from 8 health centres in Malaysia for antibodies against Orientia tsutsugamushi (OT), Rickettsia typhi (RT) and TT118 spotted fever group rickettsiae (SFGR) by using an indirect immunoperoxidase assay. A total of 51.4% patients had antibody against at least 1 of those rickettsiae. Antibody to SFGR was most prevalent (42.5%), followed by RT (28.1%) and OT (24.9%). The seroprevalences of antibodies to SFGR, RT or OT alone were 12.4, 3.6 and 4.3%, respectively. Antibodies against more than 1 species of rickettsiae were presence in …

Seroepidemiologic survey of Orientia tsutsugamushi, Rickettsia typhi, and TT118 spotted fever group rickettsiae in rubber estate workers in Malaysia.

The seroprevalence of Orientia tsutsugamushi, Rickettsia typhi, and TT118 spotted fever group (SFG) rickettsiae in 300 rubber estate workers in Slim River, Malaysia was determined in December 1996 and March 1997. In December, which was the wet season, 23.3%, 3.0%, and 57.3% of the population had antibodies detected against the three rickettsiae, respectively. The highest seropositive rate of 40% was detected for single infection with SFG rickettsiae, followed by a rate of 15.3% for both O. tsutsugamushi and SFG rickettsiae among the rubber estate workers. Subjects less than 21 years old had a …

Reemergence of Scrub Typhus Associated with Leptotrombidium akamushi Mites and Karp-Like Orientia tsutsugamushi Genotype Bacteria, Japan, 2024-2025.

Scrub typhus is a miteborne infectious disease caused by Orientia tsutsugamushi bacteria. In Japan, most cases occur in spring and autumn and are transmitted by Leptotrombidium pallidum and L. scutellare mites; summer scrub typhus, transmitted by L. akamushi mites, is rarely reported. In August 2024, a pregnant woman had scrub typhus develop after attending a fireworks event in Niigata Prefecture, Japan, resulting in fetal death. A Vietnam-related Karp-like O. tsutsugamushi genotype, distinct from the Kato type usually associated with L. akamushi mites, was detected from patient samples. Field…

Multiple Orientia clusters and Th1-skewed chemokine profile: a cross-sectional study in patients with scrub typhus from Nepal.

OBJECTIVES: Scrub typhus is an emerging infectious disease in Asia caused by Orientia tsutsugamushi (Ot). From Nepal, only scant data on the genetic epidemiology of this agent is available, and determinants of immunoregulation are poorly understood. METHODS: Patients (n = 238) referred to the National Public Health Laboratory (Kathmandu, Nepal) from all over Nepal for suspected scrub typhus were enrolled upon positive immunoglobulin (Ig)M testing between July and October 2015. From Ot 16S and 47 kD polymerase chain reaction (PCR)-positive samples, the variable domain I of the 56 kD gene was s…

High initial IgG antibody levels against Orientia tsutsugamushi are associated with an increased risk of severe scrub typhus infection.

BACKGROUND: Scrub typhus is a dominant cause of febrile illness in many parts of Asia. Immunity is limited by the great strain diversity of Orientia tsutsugamushi. It is unclear whether previous infection protects from severe infection or enhances the risk. METHODS/PRINCIPAL FINDINGS: We studied IgG antibody levels against O. tsutsugamushi at presentation in 636 scrub typhus patients using enzyme-linked immunosorbent assays (ELISA). The association between ELISA optical density (OD) and risk of severe infection was modelled using Poisson regression. OD was categorised as low (<1.0), intermedi…

Orientia tsutsugamushi uses two Ank effectors to modulate NF-κB p65 nuclear transport and inhibit NF-κB transcriptional activation.

Orientia tsutsugamushi causes scrub typhus, a potentially fatal infection that threatens over one billion people. Nuclear translocation of the transcription factor, NF-κB, is the central initiating cellular event in the antimicrobial response. Here, we report that NF-κB p65 nuclear accumulation and NF-κB-dependent transcription are inhibited in O. tsutsugamushi infected HeLa cells and/or primary macrophages, even in the presence of TNFα. The bacterium modulates p65 subcellular localization by neither degrading it nor inhibiting IκBα degradation. Rather, it exploits host exportin 1 to mediate p…

Orientia tsutsugamushi Strain Ikeda Ankyrin Repeat-Containing Proteins Recruit SCF1 Ubiquitin Ligase Machinery via Poxvirus-Like F-Box Motifs.

UNLABELLED: A rising theme among intracellular microbes is the delivery of ankyrin repeat-containing effectors (Anks) that interact with target proteins to co-opt host cell functions. Orientia tsutsugamushi, an obligate intracellular bacterium and the etiologic agent of scrub typhus, encodes one of the largest Ank repertoires of any sequenced microorganism. They have been previously identified as type 1 secretion system substrates. Here, in silico and manual sequence analyses revealed that a large proportion of O. tsutsugamushi strain Ikeda Anks bear a eukaryotic/poxvirus-like F-box motif, whi…

The Whole-genome sequencing of the obligate intracellular bacterium Orientia tsutsugamushi revealed massive gene amplification during reductive genome evolution.

Scrub typhus ('Tsutsugamushi' disease in Japanese) is a mite-borne infectious disease. The causative agent is Orientia tsutsugamushi, an obligate intracellular bacterium belonging to the family Rickettsiaceae of the subdivision alpha-Proteobacteria. In this study, we determined the complete genome sequence of O. tsutsugamushi strain Ikeda, which comprises a single chromosome of 2 008 987 bp and contains 1967 protein coding sequences (CDSs). The chromosome is much larger than those of other members of Rickettsiaceae, and 46.7% of the sequence was occupied by repetitive sequences derived from an…