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

Department of Evolution, Ecology, and Organismal Biology, The Ohio State University, Columbus, OH 43210, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 04/2009; 48 Suppl 3(s3):S203-30. DOI: 10.1086/596576
Source: PubMed


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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    • "The three other strains are named Karp (AY956315), Kato (M63382) and Gilliam (DQ485289). Information of the time and place of isolation of the reference strains was collected from Kelly et al. (2009) "
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    ABSTRACT: Orientia tsutsugamushi is the causative agent of scrub typhus, a major cause of febrile illness in rural area of Asia-Pacific region. A multi-locus sequence typing (MLST) analysis was performed on strains isolated from human patients from 3 countries in Southeast Asia: Cambodia, Vietnam and Thailand. The phylogeny of the 56-kDa protein encoding gene was analyzed on the same strains and showed a structured topology with genetically distinct clusters. MLST analysis did not lead to the same conclusion. DNA polymorphism and phylogeny of individual gene loci indicated a significant level of recombination and genetic diversity whereas the ST distribution indicated the presence of isolated patches. No correlation was found with the geographic origin. This work suggests that weak divergence in core genome and ancestral haplotypes are maintained by permanent recombination in mites while the 56-kDa protein gene is diverging in higher speed due to selection by the mammalian immune system.
    Infection Genetics and Evolution 01/2015; 31. DOI:10.1016/j.meegid.2015.01.005 · 3.02 Impact Factor
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    • "are Leptotrombidium pallidum and Leptotrombidium scuttellare, which are endemic in Asia, the Pacific region and Australia. Accordingly, scrub typhus is highly prevalent in the Asia–Pacific region including Japan, Korea, the eastern part of Russia, India, Pakistan, the southwestern Pacific islands (Kelly et al., 2009), China (Zhan et al., 2013) and Australia (Graves and Stenos, 2009). Mortality rates of up to 40% have been reported (Tamura et al., 1995), more than one million cases are recorded annually and more than one billion people are estimated to be at risk (Kim et al., 2014). "
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    ABSTRACT: There are an estimated 0.5 - 1 million mite species on earth. Among the many mites that are known to affect humans and animals, only a subset are parasitic but these can cause significant disease. We aim here to provide an overview of the most recent work in this field in order to identify common biological features of these parasites and to inform common strategies for future research. There is a critical need for diagnostic tools to allow for better surveillance and for drugs tailored specifically to the respective parasites. Multi-'omics' approaches represent a logical and timely strategy to identify the appropriate mite molecules. Recent advances in sequencing technology enable us to generate de novo genome sequence data, even from limited DNA resources. Consequently, the field of mite genomics has recently emerged and will now rapidly expand, which is a particular advantage for parasitic mites that cannot be cultured in vitro. Investigations of the microbiota associated with mites will elucidate the link between parasites and pathogens, and define the role of the mite in transmission and pathogenesis. The databases generated will provide the crucial knowledge essential to design novel diagnostic tools, control measures, prophylaxes, drugs and immunotherapies against the mites and associated secondary infections.
    International Journal for Parasitology 09/2014; 44(12). DOI:10.1016/j.ijpara.2014.08.003 · 3.87 Impact Factor
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    • "Scrub typhus can be effectively treated with antibiotics including doxycycline, chloramphenicol, and azithromycin. However, re-infection is common due to the wide variety of antigenically distinct serotypes [4]. In addition, the increasing number of patients, recurrent outbreaks, and new emergences of scrub typhus within endemic areas have recently had a profound effect on public health [5]–[8]. "
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    ABSTRACT: Background Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium. Previously, a large number of genes that encode proteins containing eukaryotic protein-protein interaction motifs such as ankyrin-repeat (Ank) domains were identified in the O. tsutsugamushi genome. However, little is known about the Ank protein function in O. tsutsugamushi. Methodology/Principal Findings To characterize the function of Ank proteins, we investigated a group of Ank proteins containing an F-box–like domain in the C-terminus in addition to the Ank domains. All nine selected ank genes were expressed at the transcriptional level in host cells infected with O. tsutsugamushi, and specific antibody responses against three Ank proteins were detected in the serum from human patients, indicating an active expression of the bacterial Ank proteins post infection. When ectopically expressed in HeLa cells, the Ank proteins of O. tsutsugamushi were consistently found in the nucleus and/or cytoplasm. In GST pull-down assays, multiple Ank proteins specifically interacted with Cullin1 and Skp1, core components of the SCF1 ubiquitin ligase complex, as well as the eukaryotic elongation factor 1 α (EF1α). Moreover, one Ank protein co-localized with the identified host targets and induced downregulation of EF1α potentially via enhanced ubiquitination. The downregulation of EF1α was observed consistently in diverse host cell types infected with O. tsutsugamushi. Conclusion/Significance These results suggest that conserved targeting and subsequent degradation of EF1α by multiple O. tsutsugamushi Ank proteins could be a novel bacterial strategy for replication and/or pathogenesis during mammalian host infection.
    PLoS ONE 08/2014; 9(8):e105652. DOI:10.1371/journal.pone.0105652 · 3.23 Impact Factor
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