Scrub-Typhus

Browning, J.S.; Coblenz, Aaron; Klein, Emil F.; Raphael, Murray

doi:10.4269/ajtmh.1945.s1-25.481

Cited by 13 publications

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“…military peaked during that war, when tens of thousands of cases and hundreds of deaths were reported among Allied and Japanese troops [32,34]. The dramatic impact of the disease in the Asia-Pacific theater of the war drove the substantial effort during and immediately after the war to prevent, control, and treat the disease [35].…”

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confidence: 98%

“…Efforts to develop and evaluate a vaccine or serodiagnostic tests would be resource intensive, requiring careful selection of representative strains. The primary purposes of this article are to review historical data on antigenic variation, including characterization of isolates found predomSince the preantibiotic era and the years of World War II in the Asia-Pacific theater, investigators have reported that scrub typhus severity and clinical presentation appeared to be strain dependent, varying tremendously from extremely mild or inapparent disease to frequently fatal disease in both humans and laboratory animals [34,[73][74][75]. The nature of the multiple antigens of Orientia strains was examined after various increasingly more sensitive assays and research tools were developed and became available.…”

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Scrub Typhus: The Geographic Distribution of Phenotypic and Genotypic Variants ofOrientia tsutsugamushi

et al. 2009

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Orientia tsutsugamushi is the etiological agent of scrub typhus, an acute, mite-borne, febrile illness that occurs in the Asia-Pacific region. Historically, strain characterization used serological analysis and revealed dramatic antigenic diversity. Eyeing a recommendation of potential vaccine candidates for broad protection, we review geographic diversity and serological and DNA prevalences. DNA analysis together with immunological analysis suggest that the prototype Karp strain and closely related strains are the most common throughout the region of endemicity. According to serological analysis, approximately 50% of isolates are seroreactive to Karp antisera, and approximately one-quarter of isolates are seroreactive to antisera against the prototype Gilliam strain. Molecular methods reveal greater diversity. By molecular methods, strains phylogenetically similar to Karp make up approximately 40% of all genotyped isolates, followed by the JG genotype group (Japan strains serotypically similar to the Gilliam strain but genetically non-Gilliam; 18% of all genotyped isolates). Three other genotype groups (Kato-related, Kawasaki-like, and TA763-like) each represent approximately 10% of genotyped isolates. Strains genetically similar to the Gilliam strain make up only 5% of isolates. Strains from these groups should be included in any potential vaccine.

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Scrub Typhus: The Geographic Distribution of Phenotypic and Genotypic Variants ofOrientia tsutsugamushi

et al. 2009

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“…Military personnel serving in areas of endemicity are at risk for contracting scrub typhus, as evidenced by over 7 decades of military disease incidence. Hundreds of American and Allied soldiers died from and several thousand became ill with scrub typhus during World War II (5,(8)(9)(10), and scrub typhus was the second leading cause of febrile illness among troops during the Vietnam conflict (5,8,(11)(12)(13) …”

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

et al. 2015

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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, which is known to recruit host cell SCF1 ubiquitin ligase machinery. We assessed the Anks for the ability to serve as F-box proteins. Coimmunoprecipitation assays demonstrated that F-box-containing Anks interact with overexpressed and/or endogenous SCF1 components. When coexpressed with FLAGAnk4_01 or FLAG-Ank9, a glutathione S-transferase (GST)-tagged version of the SCF1 component SKP1 localized to subcellular sites of FLAG-Ank accumulation. The abilities of recombinant Anks to interact and colocalize with SKP1 were F-box dependent. GST-SKP1 precipitated O. tsutsugamushi-derived Ank9 from infected host cells, verifying both that the pathogen expresses Ank9 during infection and the protein's capability to bind SKP1. Aligning O. tsutsugamushi, poxviral, and eukaryotic F-box sequences delineated three F-box residues that are highly conserved and likely to be functionally important. Substitution of these residues ablated the ability of GFP-Ank9 to interact with GST-SKP1. These results demonstrate that O. tsutsugamushi strain Ikeda Anks can co-opt host cell polyubiquitination machinery, provide the first evidence that an O. tsutsugamushi Ank does so during infection, and advance overall understanding of microbial F-box proteins. IMPORTANCEAnkyrin repeat-containing proteins (Anks) are important virulence factors of intracellular bacteria that mediate protein-protein interactions with host cell targets. Orientia tsutsugamushi, which causes a debilitating infection called scrub typhus in one of the most densely populated regions of the world, encodes one of the largest Ank armamentariums of any sequenced bacterium. This study demonstrates that O. tsutsugamushi strain Ikeda Anks also bear F-box motifs that interact with host cell polyubiquitination machinery. By proving that an Orientia-derived Ank interacts with SKP1 in infected cells, this evidences the first bona fide Orientia effector and the first example of an endogenous F-box-containing Ank-mammalian-host ligand interaction for any intracellular bacterium. Also, importantly, this work identifies key residues that are essential for microbial F-box function.T he obligate intracellular bacterium Orientia tsutsugamushi is the causative agent of scrub typhus, a potentially fatal disease transmitted to humans through the bite of an infected trombiculid mite. O. tsutsugamushi invades phagocytic cells of the immune system, as well as endothelial cells of the skin and major organs (1-4). Di...

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“…Information on the clinical presentations of these prototypes/ serotypes/genotypes is scanty. A few reports indicate that the clinical presentation and severity of scrub typhus varies with the infecting strain of O. tsutsugamushi [12]. A study from Korea highlighted the differences in clinical manifestations between Boryong and Karp genotypes of O.…”

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confidence: 99%

“…Studies conducted in mice model also demonstrated differences in the virulence among strains of O tsutsugamushi, and the strains were classified into a high virulence group (Karp, Kato and KN-3 genotypes), an intermediate virulence group (Gilliam genotype) and a low virulence group (Kuroki, Kawasaki and KN-2) [13,14]. In view of the differences in clinical manifestations with the infecting strain, it is important to investigate the distribution of genotypes across endemic areas and their association with clinical manifestations [10,12,15]. Although scrub typhus is reported from several geographic areas of India, there is a paucity of information on the occurrence of common genotypes of O. tsutsugamushi and the associated clinical presentations.…”

Section: Introductionmentioning

confidence: 99%

Occurrence of Orientia Tsutsugamushi Genotypes in Areas of Union Territory of Puducherry and Tamil Nadu State, India

K¹,

Sl²,

Kanungo³

et al. 2017

J Emerg Infect Dis

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Scrub typhus, caused by the proteobacterium, Orientia tsutsugamushi, is re-emerging in several regions of Asia, particularly in India. Severity of infection and clinical presentations are known to vary with the infecting prototype/ genotype. Hence genotypic characterization and distribution of various genotypes is of clinical and epidemiological importance. One hundred and forty five suspected scrub typhus cases, reporting to a tertiary care centre in Puducherry, India were investigated for O. tsutsugamushi specific IgM antibodies by ELISA out of which, 135 (93%) were positive. Most cases occurred post-monsoon, peaking in September, and there was a preponderance in young adults. Forty samples tested positive by Nested PCR based on 56kDa gene of O. tsutsugamushi and amplicons from PCR positive samples were sequenced. Phylogenetic tree constructed using 35 sequences (from nt 20 to nt 130) obtained in the study, along with those retrieved from NCBI site, formed two major branches; one comprising 15 sequences from this study, which aligned with Karp genotype, and the other containing 6 sequences which aligned with a sequence from Vellore, India. The second major branch had 12 sequences, which formed an independent group from the Gilliam prototype. Analysis of association of clinical manifestations with genotypes obtained in the present study showed that the sequences that formed an independent group, were associated with a wide spectrum of clinical manifestations involving multiple organs and more severe manifestations like ARDS and hypotension. The sequences, which branched with Karp prototype were associated with hepatitis, meningitis and Multi-organ disorder syndrome (MODS). The present study thus indicated that different genotypes of O. tsutsugamushi occur in southern regions of India, which were associated with various clinical manifestations. Studies on the occurrence of genotypes will help in development of diagnostic methods and vaccines to curtail the infection.

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Scrub-Typhus

Cited by 13 publications

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Scrub Typhus: The Geographic Distribution of Phenotypic and Genotypic Variants ofOrientia tsutsugamushi

Scrub Typhus: The Geographic Distribution of Phenotypic and Genotypic Variants ofOrientia tsutsugamushi

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

Occurrence of Orientia Tsutsugamushi Genotypes in Areas of Union Territory of Puducherry and Tamil Nadu State, India

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